Water and

Sodium
Homeostasis
Dr SP Gwiliza
Department of Chemical Pathology
2024
Learning Objectives
1) Briefly look at the atoms and molecules (water H2O and
electrolytes (Na and K)
2) Explain how water balance and electrolyte balance are
interdependent
3) Understand the body fluid compartments
4) Discuss risks for fluid volume deficit.
5) Discuss the role of specific electrolytes in maintaining
homeostasis
6) Discuss disorders (deficits and excesses) of water and sodium
7) Discuss the role of the management process in maintaining
fluid and electrolyte balances.
 Total Body Water—Volume and Distribution

• Average adult has:

• ≈5 L blood volume (intravascular
compartment)
• plasma volume of ≈3.0 L when the
hematocrit is ≈40%
• Factors that influence daily water and
electrolyte requirements:
• activity of the individual
• environmental conditions
• disease
• On average, an adult must take in ≈1.5 to
2.0 L of water daily to maintain fluid
https://cdn.lecturio.com/assets/Distribution-of-body-fluids.png
balance
 Organs and Tissue Water Content

Water content varies from as little as 8 percent in the teeth to as much as 85 percent in the brain.

https://www.google.com/search?q=Water+Content+of+the+Body rgans+and+Tissues. Accessed 14 December 2019

 https://ars.els-cdn.com/content/image/1-s2.0-S1472029912002329-gr3.jpg

Composition of Body Fluids

 Electrolytes

● Electrolytes are chemicals that conduct electricity when mixed with water.

● An anion is an ionic species with a negative charge.

● A cation is an ionic species with a positive charge.

● The chemical species may be a single atom or a group of atoms.

● Electrolytes regulate nerve and muscle function, acid base, blood pressure, and tissue repair.
 Common electrolytes
Cations Anions
Lithium Li+ Fluoride Fl-
Sodium Na+ Chloride Cl-
Ammonium NH4+ Bromide Br-
Potassium K+ Phosphate PO42-
Magnesium Mg2+ Nitrite NO2-
Calcium Ca2+ Nitrate NO3 -

● Anions are typically larger than cations because they have extra electrons around them
Electrolytes distribution in between different Fluid Compartments
Sodium
Functions of Sodium
• Transmission and conduction of nerve impulses

• Responsible for osmolarity of vascular fluids

• Regulation of body fluid levels

• Sodium shifts into cells and potassium shifts out of the cells
(sodium pump)

• Assists with regulation of acid-base balance  combines

with Cl or HCO3.
 • Total body sodium is: 40 - 50mmol/kg body mass

• ± 70% freely exchangeable, majority in

ECC

• ± 30% complexed in bone

Distribution • The 70% freely exchangeable sodium distribution:

Balance of • ± 60% in ECF (135 - 145mmol/l)

Sodium • ± 10% in ICF (4 - 10mmol/L)

• Most cell membranes are relatively impermeable

to sodium

• Trans cell membrane gradient maintained by Na-K-

ATPase pump ***
 Balance of Sodium Intake and Excretion

Intake: Salt (NaCl) is 100 – 200mmol/24hrs, absorbed via the gut active transport

• ± 1000 mmol/24hrs secreted into the gut with majority being reabsorbed 
failure results in GIT loss of sodium and imbalance)

Excretion: Kidney is the major organ of sodium excretion = Urine± 90%

• Sweat and Stool ± 10%
• Obligatory loss via kidneys, skin & gut <20 mmol/ 24hrs (any excess normally
lost in urine)
Homeostasis of water and electrolytes involves various organs/ tissues and systems
Hypothalamic
Osmoreceptors
• [Na+] is the major determinant of ECF
osmolality
• An increase in ECF[Na+] results in
water movement from cells into the
ECF.
• This leads to intracellular
dehydration.

• Similarly, with a decrease in the

ECF[Na+], water passes from the ECF
into cells
• This leads to swelling of the cells.
Hypothalamic Osmoreceptors
• Sensitive to any acute small changes
in plasma osmolality
• Responding to a change of as little as 1%
• Cell volume receptor
• Hypothalamic cell shrinkage activates the
osmostat
• It controls:
• ADH Secretion
• Thirst Sensation
Renal handling of
Sodium
• ± 2500 mmol/24hrs filtered by the glomeruli
• Followed by reabsorption by renal tubules
• <5% of the filtered reaching the distal tubules
where fine control of Na+ balance occurs
[aldosterone effect]

• Na+ excretion in the urine is ±150 – 250 mmol/day

• Major regulative hormones of sodium excretion:

• - Aldosterone
• - ANP

• Character of sodium excretion by kidney:

• -No intake, no excretion
• -More intake, more excretion and less intake, less
excretion
Osmolality vs Osmolarity
• These measures are technically different but functionally the same.

• Osmolality = total number of dissolved particles in 1kg solution

(Osmol/kg)

• Determined (measured) using the freezing point depression

osmometer.

• Osmolarity = total number of dissolved particles in 1L solution

(Osmol/L)

• Determined (calculated) by various formulas using solute levels in

to ECF.
Formula for calculated
osmolarity:
• Osmol = 2[Na+] + [Urea] + [Glucose]

• The factor 2 is to allow for the major anions binding the Na

• Note that measured Osmolality includes calculated osmolarity +

concentrations of other solutes present in plasma.

• Therefore, Osmolality cannot be less than osmolarity.

• If osmolarity > osmolality suspect:

• - laboratory error
• - calculation error
https://img.brainkart.com/imagebk32/oBRsUy8.jpg
Urine : Plasma osmolality ratio:

• Urine osmolality varies depending on the state of hydration and renal function

• Urine osmol: Plasma osmol ≈ 1 (1.5 – 1.8)

• In Dehydration:
• Ur osmol: Pl osmol ≥1 (usually > 2 x)
• Urine osmolality will be maximal approaching ~ 1000 mOsmol/kg.

• In Overhydration:
• Ur osmol: Pl osmol ≤ 1
• Urine osmolality will be close to maximal dilution ± 50 – 100mOsmol/kg
Causes of
Hyperosmolality
• 1. Hypertonic dehydration (usually with hypernatraemia)
• 2. Diabetes mellitus (various reasons)
• 3. Renal failure
• 4. Lactic acidosis
• 5. Hepatic failure
• 6. Sepsis
• 7. Intoxication e.g., alcohol, salicylates, barbiturates
• 8. High protein intake

• Indications for determination of plasma osmolality include:

• Interpretation of low plasma sodium

• Assessment of the hydration status of patients
• Useful in water deprivation test
Osmolal gap (Osmolar Gap)
• Difference between measured osmolality and calculated osmolarity

• Osmolal gap = Measured osmolality – calculated osmolarity

• Normal: 5 - 10mOsm/kg

• The osmolal gap shows the presence volatile substances (osmotically

active) or a change in the fractional water content.

• Examples are:
1. Uremia
2. Diabetes mellitus - especially during ketoacidosis
3. Lactic acidosis
4. Hyperlipopoteinaemias
5. Hyperproteinaemia
6. Ethanol, methanol or ethylene glycol, acetone intoxication
7. Glycine
8. Mannitol
 • ECF osmolality = ICF osmolality

• Therefore, ECF osmolality is a guide to ICF osmolality

• Changes in water content without solutes  alter osmolality

• Changes in ECF (plasma) osmolality  influence water movement

Water and ECF across cell membrane  influence ICF osmolality  may affect cell
function

osmolality • ECF (plasma) osmolality can be used as an indicator of ECF volume:

• In pure water loss  Pl-Osmolality = ↑ ECF volume or dehydration

• In pure water gain  Pl-Osmolality = ↓ ECF volume or over-

hydration
Mechanism in Water loss from ECF (dehydration)  ↑ ECF osmolality
↓
restoration of Water movement from ICF to ECF

water and ECF ↓

Stimulation of thirst center  ↑ water intake

osmolality ↓
Stimulation of ADH release  renal water reabsorption
homeostasis ↓
Stimulation of RAAS
↓
Increased Aldosterone
↓
Reabsorption of Sodium and Water
Stimulation of
RAAS
• The kidneys produce renin in
response to low blood pressure
or low plasma Na+
concentration.
• Renin acts on
Angiotensinogen in plasma to
form Angiotensin I which is
subsequently converted to
Angiotensin II in the lungs by the
action of angiotensin-converting
enzyme (ACE).
• Angiotensin II acts as a
neurotransmitter on different
organs to produce changes that
restores blood pressure and Na+.
Disorders of Water and
Sodium Balance
Disorders of • Reduced or increased intake is a very rare cause.

Water and • Reduced or increased loss (imbalance between

intake and loss) is common

Sodium Balance
Water Loss/
Dehydration
 • Clinically known as dehydration

• Occurs due to inadequate intake or excessive loss of

water

Water • Depending on the ratio of Water to Na+ lost this can

be classified as:
Depletion:
• a) Isotonic fluid loss: (Equimolar loss of H2O and Na+
Dehydration  Normal S-Osmolality

• b) Hypotonic fluid loss: (H2O loss > Na+ loss)  ↑S-

Osmolality
 Hypotonic fluid loss

• Due to pure water loss

Causes of Hypotonic fluid loss

• Diabetes Insipidus (DI)

• Osmotic diuresis (eg. diabetes mellitus)

• Excess sweating, fever or exercise in a hot climate

• Hyperventilation or assisted ventilation with unhumidified air

• Cessation of water intake with ongoing obligatory water loss eg.in infants, elderly or
unconscious patients.
Effects of Hypotonic fluid
loss

• Water in excess of Na+ is

lost from the ECF 
ECF[Na+] rises  higher
osmolality  movement of
water from the ICF into the
ECF.
 • In the brain is cerebral dehydration resulting in
confusion.

Effects of • Hypothalamic Osmoreceptors evokes ADH and

thirst response.

Hypotonic fluid • Urine becomes maximally concentrated, with urine

loss osmolality approaching 1000 mosmol/kg (except
when the cause of the water loss is diabetes
insipidus).

• Signs of circulatory collapse (tachycardia, low BP,

oliguria) are less pronounced, & occur later
• Movement of water from ICF to ECF minimizes
the depletion in blood volume
 • If the loss continues, volume will be depleted and result in renal
under perfusion evoking renin release, which, via the angiotensin
pathway, stimulates aldosterone secretion.

• Aldosterone promotes Na+ uptake by the distal tubule and results in

an extremely low urine [Na+] (<10mM).
Effects of • This is a valuable clue that the hypernatraemia is due to water
Hypotonic depletion rather than excess salt intake, since in the latter condition,
urine [Na] is very high (>100mM).
fluid loss • Treatment

• Fluids with a low Na+ content should be used for replacement -

either water by mouth, or, if unable to drink, 5% glucose or 1/2N
NaCl intravenously.

• Beware of over-rapid correction if long-standing, since accumulated

osmolytes pose the risk of iatrogenic cerebral oedema.
 Isotonic fluid loss
Happens when water loss is accompanied by an equivalent amount of Na+

• Causes of Isotonic fluid loss

• Haemorrhage

• Burns

• GIT loss (diarrhoea, vomiting, fistula)

• Renal loss (diuretics)

• Effusion of ECF into body spaces (hematoma, ascites, pancreatitis)

 • No immediate change in plasma [Na+], therefore no
movement of fluid from the ICF.

• Thus, cerebral dehydration is not a problem.

Effects of
Isotonic Fluid • However, since all the fluid lost comes from the ECF,
circulatory collapse is more pronounced than in
Loss hypotonic fluid loss.

• Patients can present shocked, pale with tachycardia and

hypotension.

• GFR falls  fall in urine output, and progressive rise in

plasma urea and creatinine.
 • The fall in renal perfusion triggers aldosterone release via
the renin/angiotensin mechanism (except in Addisons
disease)

• As with hypotonic fluid loss, urine is therefore highly

Effects of concentrated, with a very low [Na] (<10mmol/l).

Isotonic Fluid • Since plasma osmolality is unchanged, there is no osmotic

Loss stimulus for early ADH release such as occurs in hypotonic
fluid loss. (Remember osmostat)

• Treatment
• Provided the patient has not development acute renal
failure, consists of rapidly replacing the ECF deficit with
intravenous isotonic saline (0.9%NaCl).
 • Can also be sub-divided into:

• pure water overload

• isotonic water overload.

Water excess in ECF (Overhydration)  ↓ ECF

osmolality

Water movement from ECF to ICF

Overhydration ↓
Inhibition of thirst centre ↓ water intake
↓
Inhibition of ADH release  diuresis
↓
Stimulation of ANP release  Natriuresis +
diuresis
 Pure Water Overload
• Water intoxication is rare, kidneys have capacity to excrete excess
water load.
• Requires intact renal function
• Failure to excrete a water load results in immediate dilutional
hyponatraemia
• cerebral oedema

Causes of pure water overload

• Water intake at a rate in excess of the kidney’s ability to excrete it.
• mental disorder (psychogenic polydipsia)
• Water intake in patients with salt-losing conditions.
• salt-losing nephritis
• diuretics that impair tubular salt reabsorption
• Syndrome of inappropriate ADH (SIADH)
 MANAGEMENT OF PURE
WATER OVERLOAD
• Restriction of water intake
• Intravenous hypertonic saline (5% NaCl) or mannitol will rapidly remove
intracellular water

• Two complications may arise during treatment:

• Rapid infusion on hypertonic NaCl can overload the vascular bed (ECF)
and lead to pulmonary oedema
• Over-rapid correction of plasma osmolality may cause cerebral
dehydration,
• long-standing hyponatraemia and the brain has responded by
decreasing its level of osmolytes
• CENTRAL PONTINE MYELINOSIS
• Acute, potentially fatal neurological condition
• Occurs if chronic hyponatraemia is too rapidly corrected
• As a general guide, it should not be increased by >1mmol/l/hr, or
10mmol/l/day
Isotonic Water Overload
• Accumulation of water is accompanied by an equivalent retention of
Na+
• ECF bears the entire brunt of the fluid overload - no osmotic force to
drive excess fluid into the cells
• Clinical features: hypertension, or peripheral and/or pulmonary oedema
• No neurological manifestations from intra-cerebral water shifts

• Causes of isotonic fluid overload

• Administration of excess isotonic fluid in the presence of impaired
renal function
• Hyperaldosteronism: Primary or Secondary
Primary hyperaldosteronism
(Conn's syndrome)
• This is autonomous secretion of aldosterone, by an adrenal adenoma.

• Aldosterone acts on the distal tubules resulting in excessive Na+ and water reabsorption.

• Absorption of Na+ in concomitant loss of K+ and H+.

• There is generally a hypokalaemic alkalosis, with normal to slightly increased Na+

• Plasma renin levels are appropriately suppressed, and the high plasma aldosterone
levels.

• Patients are typically hypertensive, but since ECF volume expansion is limited by ANF,
oedema is not a feature.
Secondary hyperaldosteronism
• Excessive aldosterone secretion in response to inappropriately high renin
secretion
• Causes:
1. A renin-secreting tumor (rare).
2. A disturbance in the blood supply to one or both kidneys, eg. renal
artery stenosis
3. Abnormal shift of fluid in the ECF i.e., from plasma into the interstitial
space. (commonest cause)
• Depleted plasma volume stimulates renin secretion
• Despite a depleted plasma volume, total ECF volume is grossly
expanded.
• Associated with congestive cardiac failure, liver cirrhosis, nephrotic
syndrome, protein-losing enteropathy and protein malnutrition
(kwashiorkor)
• Clinically presents with severe peripheral oedema, hyponatraemia
• Treatment: reversing the underlying condition, diuretic therapy and
limiting salt intake
 • Cerebral dehydration causes the brain to pull away from the
meninges, rupturing meningeal vessels.

• Cerebral overhydration can result in cerebral swelling (oedema)

Effects of resulting in catastrophic compression of the brain against the rigid vault
of the skull.

Hydration • Affected individuals exhibit neurological symptoms; from altered

Status on the behavior, irritability, and impaired level of consciousness, to convulsions
and coma.

Brain • In Chronic abnormalities, the brain adapts to these water shifts by

appropriately altering its content of 'osmolytes'.

• These heterogeneous collection of small molecules, including ions

and organic compounds, accumulate in neuronal cells exposed to high
ECF osmolality, minimizing water loss.

• Osmolytes fall in brain cells chronically exposed to low ECF osmolality,

thereby minimizing water influx.
 The effect of hypotonic overhydration on the brain, adaptive changes and the effects of rapid
correction. T=tonicity, N=normal

Central Pontine Myelinosis is an acute neurological condition that occurs if chronic

hyponatraemia is too rapidly corrected. (demyelination of the pons)
The effect of hypertonic dehydration
on the brain, adaptive changes and
the effects of rapid correction.
T=tonicity, N=normal
• Severe water depletion induces
cerebral dehydration, which may
cause cerebral haemorrhage through
tearing of blood vessels.
• In the short term, cerebral
shrinkage is mitigated somewhat by
movement of extracellular ions into
cerebral cells, causing an osmotic
intracellular shift of water.
• If dehydration persists, brain cells
adapt by synthesizing osmotically
active organic compounds
(‘osmolytes’), and cerebral oedema
may then follow rapid fluid
replacement
Effects of hyponatremia on the brain and adaptive mechanism.
Sodium Disorders
Sodium
Depletion
Pseudohyponatraemia
 Pseudohyponatraemia

• Water contributes 93% to the volume of normal plasma.

• 7% is mainly protein and lipid contributing.

• Plasma lipid can increase enormously, to account for 5 or even 10% of plasma volume.

• Since [Na+] in the aqueous phase of plasma is normal, there is no tendency for fluid shifts.

• Analytical methods that measure Na+ content of a fixed volume of plasma yield misleadingly low [Na+] (pseudohyponatraemia)

• Osmolality depends on solute concentration in the aqueous phase of plasma therefore osmolality is not affected in pseudohyponatraemia.

• Lipid can be removed by ultracentrifugation, and the Na+ measurement repeated on the infranatant.
 • Seriously ill patients often develop a mild hyponatraemia.

• Sick cell syndrome or cell sickness syndrome is a condition

characterised by reduced functioning of the cellular Na/K ATPase.
Sick Cell • The clinical result is a rise in blood K+ level and drop of blood Na +
Syndrome •
levels.
due to the failure of the Na/K ATPase to extrude Na+.

• This form of hyponatraemia requires no treatment beyond that of

the underlying condition.
Sodium
Excess
GrepMed Recommended Text: Nephrology Secrets - https://amzn.to/2Z74DhY
The fractional excretion of sodium (FENa) is a measure of the percentage (%) of sodium
excreted in the urine versus the sodium reabsorbed by the kidney.

It is measured in terms of plasma and urine sodium, rather than by the interpretation of
urinary sodium concentration alone, as urinary sodium concentrations can vary with water
resorption.

Therefore, the urinary and plasma concentrations of sodium must be compared to get an
accurate picture of renal clearance.

https://slideplayer.com/slide/4337117/
Practical Issues

• When to measure plasma Na+

• Dehydrated patients or those with a history of fluid loss

• Patients receiving fluids intravenously, especially infants, the elderly and the
unconscious.

• Patients with unexplained alteration in level of consciousness, confusion or irritability.

 Interpreting plasma Na+
• An isolated [Na+] 125mmol/L is of little clinical value.
• Interpretation requires:
• The history - has there been:
• a head injury to suggest SIADH?
• diarrhoea and/or vomiting?
• polyuria or polydipsia to suggest diabetes (mellitus or insipidis)?
• diuretic therapy?
• The clinical examination
• level of consciousness?
• hydration status - are there signs of water overload (oedema, distended neck veins, hypertension, pulmonary
oedema) or dehydration (loss of skin turgor, dry mouth, tachycardia, low BP, concentrated urine, oliguria)?
• rapid weight changes, fluid intake/output recordings?
• features of cardiac failure, liver cirrhosis or nephrotic syndrome, to suggest secondary
• hyperaldosteronism?
• Urine findings
• appearance - dilute or concentrated?
• osmolality?
• [Na+] concentration?
• any glucose or protein?
• Blood findings
• haemoconcentration (increased haemoglobin and protein)?
• renal function (urea and creatinine levels)?
• milky appearance (lipidaemia)?
• K+ abnormalities (Addisons or primary aldosteronism)?
• low cortisol or high TSH to account for SIADH?
The end