CLS 382 - Lecture 10

Electrolytes I - Water and Sodium Balance

 What are electrolytes?
• Fluid and electrolyte balance is central to the management of any patient who is
seriously ill.
• An electrolyte is a substance that produces an electrically conducting solution when
dissolved in a polar solvent, such as water.
• The dissolved electrolyte separates into cations and anions, which disperse uniformly
through the solvent.
• An anion is an ion with more electrons than protons, giving it a net negative charge
• A cation is an ion with fewer electrons than protons, giving it a positive charge.
• The primary electrolytes are sodium (Na+), potassium (K+), calcium (Ca2+), magnesium
(Mg2+), chloride (Cl−), hydrogen phosphate (HPO42−), and hydrogen carbonate
(HCO3−).
• Measurement of serum sodium, potassium, urea and creatinine, frequently with
bicarbonate, is a frequently requested biochemical profile and provides a lot of
information about a patient’s fluid and electrolyte status and renal function.
• A request for measurement of serum ‘electrolytes’ usually generates values for the
concentration of Na+ and K+ ions, together with HCO3¯ ions.
 Body fluid compartments
• Subtle, complex electrolyte balance is needed between intracellular and extracellular environments.
• This maintenance of precise osmotic gradients of electrolytes is important for various functions.
• Various mechanisms exist to keep the concentrations of different electrolytes under tight control.
• Sodium (Na+) is the principal extracellular cation, and makes the largest contribution to the total
plasma osmolality. Potassium (K+) is the major intracellular cation.
• The main anions intracellularly are protein and phosphate. Whereas in the ECF chloride (Cl¯) and
bicarbonate (HCO3¯) predominate.
 ADH (AVP)
• Water excretion by the kidney is very tightly controlled by arginine vasopressin (AVP; aka
antidiuretic hormone, ADH); synthesized by the hypothalamus in the brain.
• It is then stored (and secreted) from the posterior pituitary gland in response to reductions
in plasma volume or increases in the plasma osmolality.
• The 2 primary functions of ADH are: 1) retain water in the body, 2) constrict blood vessels
• ADH regulates the body's retention of water by acting to increase water reabsorption in the
kidney's collecting ducts. If the RAAS is abnormally active, blood pressure will be too high.
• There are many drugs that
interrupt different steps in
this RAAS system in aim to
lower blood pressure.
• These drugs are one of the
primary ways to control high
blood pressure
(hypertension), heart
failure, kidney failure, and
harmful effects of diabetes
(antihypertensive drugs, e.g.

➢ Angiotensin‐converting enzyme (ACE) inhibitors

➢ Angiotensin II antagonists (AIIAs)
 Renin-angiotensin-aldosterone system -RAAS-
• The renin–angiotensin–aldosterone system (RAAS) is a hormone system that regulates:
i. plasma Na+ concentration
ii. arterial blood pressure

• The RAAS system can be activated when there is:

i. a loss of blood volume
ii. a drop in blood pressure (such as in hemorrhage or dehydration).
• When the plasma Na+ concentration is lower than normal or the renal blood flow is
reduced;
1) Signals are received by the juxtaglomerular cells in the kidneys in order to convert
prorenin (an intracellular protein) into renin
2) Renin is then secreted directly into the circulation. It cuts off a short peptide (10
amino acids long) from a plasma protein known as angiotensinogen. This short,
cleaved peptide is known as angiotensin I
3) Angiotensin I is then converted, by the removal of 2 amino acids, to form
angiotensin II, by the enzyme angiotensin-converting enzyme (ACE)
ACE is found in the endothelial cells of small capillaries throughout the body, within the
lungs and the epithelial cells of the kidneys.
• Angiotensin II is the major bioactive product of the renin-angiotensin system; a potent
vaso-active peptide that:
1) causes arterioles to constrict, resulting in increased arterial blood pressure
2) stimulates the secretion of the hormone aldosterone from the adrenal cortex
3) stimulates AVP secretion
4) has a direct effect on the proximal tubules to increase Na+ reabsorption.
• Aldosterone causes the tubular epithelial cells of the kidneys to:
1) increase the reabsorption of Na+ ions from the tubular fluid back into the blood
2) while at the same time causing them to excrete K+ ions into the tubular fluid which will
become urine.

• The prevention of sodium losses via the

urine, and the correction of any deficit by
consuming salt act together to increase
blood pressure.
• These actions are opposed by atrial
natriuretic peptide (ANP) which is secreted
from the atria of the heart in response to
stretch caused by an excessive blood
volume.
 Who to check Na+ levels for?
• The measurement of serum Na (with other electrolytes) is routinely requested in
everyday clinical practice (e.g. outpatients, pre-operative, etc..)
• Reference range = (135-145 mmol/L)
• However, there are several indications when measurements are considered;
i. Patients with significant cardiac, renal or liver disease
ii. Seriously ill patients, including those who are unconscious or debilitated
iii.Patients receiving IV fluids or parenteral nutrition
iv. Patients on drugs that may affect serum Na levels. For instance diuretics; a very
common cause of hyponatremia
v. Patients with uncontrolled diabetes mellitus
vi. Patients with polyuria or polydipsia

• In most cases, an abnormal level may not require urgent action. Indeed
enthusiastic treatment of hyponatremia or hypernatremia might be dangerous
• However, clinicians are ought to look out for patterns, in order to adjust therapy
(e.g. fluid restriction, adjusting IV fluids or diuretic doses ..etc)
• If serum Na levels are ≤120 mmol/L or ≥160 mmol/L, then active treatment should
be recommended
 Hypertension

If hypertension is left untreated, patients are at risk of several complications, that may lead
to end-organ damage. These may include:
➢ stroke
➢ left ventricular hypertrophy (leading eventually to heart failure)
➢ chronic kidney disease
➢ retinopathy
Schmieder RE. End organ damage in hypertension
Dtsch Arztebl Int. 2010;107(49):866-873
 Osmolality
• Remember that a concentration is a ratio of two variables: the amount of solute
(e.g. sodium), and the amount of solvent (water).
• A concentration can change because either or both variables have changed.
• For example, a sodium concentration of 140 mmol/L may become 130 mmol/L
because the amount of sodium in the solution has fallen or because the amount of
water has increased.
• ECF and ICF compartments are separated by semipermeable membranes through
which water moves freely.
• Osmotic pressure must always be the same on both sides of a cell membrane, and
water moves to keep the osmolality the same, even if this water movement causes
cells to shrink or expand in volume.
• The osmolality of the ICF is normally the same as the ECF. The two compartments
contain isotonic solutions.
• The osmolality of a solution is expressed in mmol solute per kilogram of solvent,
which is usually water.
• In man, the osmolality of serum (and all other body fluids except urine) is around
285 mmol/kg.
 Osmolality
• Osmolality is dynamic and will fluctuate as the body responds to and corrects
temporary water imbalances.
• Serum and urine osmolality tests must be evaluated in the context of the person's
signs and symptoms and along with the findings of other tests, such
as sodium, glucose, and blood urea nitrogen (BUN).
• Osmolality results are not diagnostic; they suggest that a person has an imbalance,
but they do not pinpoint the cause.
• In general, increased serum osmolality may be due to either decreased water in
the blood or increased solutes.
• Osmolality of a serum or plasma sample can be measured directly, or it may be
calculated if the concentrations of the major solutes are already known.
• There are many formulae used to calculate the serum osmolality. Clinically, the
simplest is:
Serum osmolality [mmol/kg] = 2 x serum sodium [mmol/L]
• This simple formula only holds if the serum concentration of urea and glucose are
within the reference intervals.
• When an apparent difference is observed between the measured and calculated
osmolality, it is referred to as the osmolal gap.
Psuedohyponatremia
• Hyponatraemia could be reported in patients with severe
hyperproteinaemia or hyperlipidaemia, as the increased amounts of
protein or lipoprotein occupy more of the plasma volume than usual, and
the water is less.
• Na and other electrolytes are distributed in the water fraction only, and
these patients have a normal sodium concentration in their plasma water.
• However, many methods used will measure Na concentration in the total
plasma volume, and take no account of a water fraction that occupies less
of the total plasma volume than usual.
• The low sodium result obtained in these circumstances is an artefact
called pseudohyponatraemia, which is suspected if there is a discrepancy
between what appears to be hyponatraemia and the symptoms that are
expected due to the low Na concentration (e.g. a patient with a Na= 110
mmol/L who is completely asymptomatic).
• A normal serum osmolality in a patient with severe hyponatraemia is
strongly suggestive of pseudohyponatraemia.
• This can be assessed formally by calculating the osmolal gap
Osmolal gap
• A serum osmolal gap of greater than 10 is
considered abnormal and indicates the
presence of an osmotically active substance
in the blood.
• When someone has an increased osmolal
gap, a toxic ingestion, such as methanol, is
suspected, and the size of the gap is
proportional to the amount of toxin.
• Other common causes of an elevated
osmolal gap are alcoholic ketoacidosis,
kidney failure, diabetic ketoacidosis, and
shock.
• During monitoring of treatment, the
osmolal gap, and findings such as a low
sodium level, return to normal.
 Serum osmolality
Conditions that can cause increased
serum osmolality
➢ Toxic ingestion (e.g.) alcohols or aspirin
(salicylates)
➢ Dehydration
➢ Increase blood glucose
➢ Increased blood sodium
➢ Increased nitrogen waste products in the
blood (uremia)
➢ Stroke or head trauma that may lead to
decreased antidiuretic hormone (ADH)
➢ Kidney disease
➢ Mannitol therapy--used in the treatment
of brain swelling (cerebral edema)
➢ Shock (inadequate blood flow; a medical
emergency recognized by markedly low
blood pressure with evidence of poor
function of the brain, kidneys, heart,
and/or liver)
Conditions that can cause decreased
serum osmolality
➢ Excess hydration (drinking excessive
amounts of water, water retention or
decreased ability of the kidneys to
produce urine)
➢ Decreased blood sodium
➢ Increased ADH secretion
Water intoxication, also known as
water poisoning
hyperhydration (overhydration)
water toxemia
is a potentially fatal disturbance
in brain functions that results when the
normal balance of electrolytes in the
body is pushed outside safe limits by
excessive water intake.
 Urine osmolality
Conditions that can cause increased Conditions that can cause decreased
urine osmolality urine osmolality

➢ Dehydration ➢ Diabetes insipidus

➢ Congestive heart failure ➢ Drinking excess fluids
➢ Increased sodium ➢ Increased blood calcium
➢ Inappropriate ADH secretion ➢ Decreased blood potassium
➢ Adrenal insufficiency (Addison's ➢ Kidney disease or kidney failure
disease)
➢ Liver damage
➢ Shock
➢ Glucosuria (from uncontrolled
diabetes)