WATER AND ELECTROLYTES

22/11/2014

50 to 60% of human body is water (Decrease with age)

Body Fluid Compartments

28 L

15 L

93% of plasma (5 L) volume is water and 7% is proteins.

Water balance
IN TAKE

BEVERAGES
= 1500 mL
WATER IN FOOD = 600 mL
METABOLIC WATER= 400 mL

TOTAL

= 2500 mL

OUT PUT

URINE
= 1500 mL
SKIN LOSS
= 500 mL
(SWEAT / INSENSIBLE)
LUNGS
= 400 mL
FECES
= 100 mL
TOTAL
= 2500 mL

Water balance
-To be in balance, the quantities of fluids and
electrolytes leaving the body should be equal to the
amounts taken in.

- Electrolytes are molecules that release ions in water.

Anything that alters the concentrations of electrolytes
will also alter the concentration of water, and vice versa.

Water balance
Controlling input (thirst center)
Controlling out put ( ADH)
Electrolyte balance

Water balance
Balance of Water content of ICF and ECF is controlled
the osmolality between the two must be maintained.
The movement of water is controlled by
hydrostatic and
colloid osmotic pressure

Water balance

Osmolality
Physical property of solution
Mmol/kg of solvent (plasma)
Both sensation of thirst & ADH secretion are stimulated
by hypothalamus in response to increase smolality ( it
is parameter to which hypothalamus is response)
Affected also by the Na concentration( 90% of osmotic
activity is related to Na)
Normal range 275 295mSm/kg
Smolality is regulated by changes in water balance
But volume is regulated by changes in Na balance

Regulation of smolality
Osmoreceptors in hypothalamus response to
small changes(increase) in smolality:
Sensation of thirst
consume more fluids
increasing the water content of the ECF
and decreasing the osmolality of the plasma

increase of smolality :
ADH secretion is stimulated
Increases renal reabsorption of water

Water Depletion (Hypovolemia)

occurs in variety of diseases like diarrhea,
vomiting, fever, burns etc.
Isotonic : loss of both water and electrolytes
Dehydration : Loss of water
The loss of water increases plasma osmolality and
causes dehydration of ICF specially of CNS tissues as
water moves from ICF to ECF which more dangerous
than ECF dehydration & may result in coma and death
in severe cases.

Response to water depletion

Body responds with stimulation of thirst which
increases the intake of water and stimulation
of ADH release which increases water
reabsorption from kidneys thereby restoring
the water balance.

HOMEOSTATIC CORRECTION WATER

DEPLETION

Regulation of body water Volume

Kidneys
Capillary pressure forces fluid through the walls
and into the tubule
At this point H2O or electrolytes are then either
retained or excreted
The urine becomes more dilute or more
concentrated based on the needs of the body

 Controlling of both Na and water are

interrelated in controlling blood volume
ADH
Renin- Angiotensin 11 aldosterone system is
stimulated by decrease of blood volume or
decrease blood pressure

Regulation of Fluid Volume

Antidiuretic hormone (ADH)

Also called arginine vasopressin hormone (AVP)

Produced by the hypothalamus
Stored in the pituitary gland
Restores blood volume by increasing or decreasing
excretion of water
Increased osmolality or decreased blood volume
stimulates the release of ADH

Then the kidneys reabsorb water

Also may be released by stress, pain, surgery, and
some meds

Regulation of Fluid Volume

Renin-angiotensin-aldosterone system
Renin secreted in kidney ( glomeruli)
Amount of renin produced depends on blood flow and
amount of Na in the blood
It converts angiotensinogen into angioensin 1 which
become angiotensin 11

Produces angiotensin II (vasoconstrictor)

Angiotensin causes peripheral vasoconstriction
Angiotensin II stimulates the production of
aldosterone

Regulation of Fluid Volume, cont.

Aldosterone
Secreted by the adrenal gland response to angiotensin II
The adrenal gland may also be stimulated by the amount
of Na and K + in the blood
Causes the kidneys to retain Na and H2O
Leads to increases in fluid volume and Na levels
Decreases the reabsorption of K+
Maintains B/P and fluid balance

Regulation of Fluid Volume, cont

Atrial natriuretic peptide or factor (ANP) (ANF)
Cardiac hormone
Released in response to increased pressure in the atria
(increased blood volume)
Opposes the renin-angiotensin-aldosterone system
Stimulates excretion of Na and H2O
Suppresses renin level
Decreases the release of aldosterone
Decreases ADH release
Reduces vascular resistance by causing vasodilatation

FLUID VOLUME DEFICITE

Hypovolemia: isotonic
extracellular fluid deficit
Deficiency of both
water & electrolytes
Caused by decreased
intake, vomiting,
diarrhea, fluid shift

Dehydration: hypertonic
extracellular fluid deficit
Deficiency of water
Caused by water loss
related to high blood
glucose, inadequate
ADH production, high
fever, excess sweating

FLUID VOLUME EXCESS

Extracellular: isotonic fluid
excess
Excess of both water and
electrolytes
Caused by retention of
water and electrolytes
related to kidney disease;
overload with isotonic IV
fluids

Intracellular: water excess

Excess of body water
without excess electrolytes
Caused by over-hydration in
the presence of renal failure;
administration of D5W

 WATER EXCESS : occurs rarely specially in

those patients who are on Intravenous(IV)
fluids and in some Psychiatric diseases.
The excess of water decreases plasma
osmolality and causes over hydration.

HOMEOSTATIC CORECTION OF WATER

EXCESS

ABNORMALITY OF ADH (DIABETES

INSIPIDUS)
Rare disease of posterior pituitary resulting in loss of
ADH secretion.
The loss of water increases plasma osmolality and
causes dehydration of ICF.
Body tries to respond with stimulation of thirst which
increases the intake of water but due to disease of
ADH there is no increase reabsorption of water from
the kidneys so the balance is not restored and patient
continues to excrete a large amount of urine although
he is dehydrated

ABNORMALITY OF ADH (DIABETES INSIPIDUS)

Fluid shifting
1st space shifting- normal distribution of fluid
in both the ECF compartment and ICF
compartment.
2nd space shifting- excess accumulation of
interstitial fluid (edema)
3rd space shifting- fluid accumulation in areas
that are normally have no or little amounts of
fluids (ascites)

Diagnostic Tests for water electrolyte

balance
Urine studies
Urine pH Urine specific gravity
Urine osmolarity
Urine creatinine clearance
Urine sodium
Urine potassium

Diagnostic Tests for water electrolyte

balance
Blood Studies

Serum Hematocrit = 40-54%/men, 38-47% for

women
Serum Creatinine = 0.6 1.5 mg/dl
BUN = 8-20 mg/dL
Serum osmolality
Serum Albumin 3.5-5.5 g/dL
Serum Electrolytes

Electrolytes
Anions : Negatively charged

ClHCO3H2PO3H2PO4-

Cations: positively charged

Na
K
Mg
Ca

COMPOSITION OF THE BODY FLUIDS

EXTRA CELLULAR FLUIDS
ANIONS
Cl =100 mmol/L
HCO3=26mmol/L
ORGANIC
IONS =3 mmol/L
PHOSPHATE = 1 mmol/L
SULPHATE = 0.5 mmol/L
PLASMA PROTEINS= 16
mmol/L

CATIONS
SODIUM = 140
mmol/L
K+ = 4.5 mmol/L
Ca 2+ = 1.3
mmol/L
Mg 2+ =
0.7mmol/L

INTRACELLULAR FLUIDS
ANIONS
PHOSPHATE = 126
HCO3 = 10
SULPHATE = 10
ORGANIC IONS = 05
PROTEINATE = 40
As mmol / Kg of WATER

CATIONS
K+ = 165
Mg+ = 14
Na+ = 12
Ca+ = very less
As mmol / Kg
of WATER

Sodium
Most abundant ECF cation (90%)
Determine the smolality of the blood
Na/K ATPase pump control active transport of
Na into out side the cell
3 Na ions exchanged for 2 K ions

Na level regulation
Intake & excretion of water
Renal regulation
1. Intake of water in response to thirst as
stimulated or suppressed by plasma smolality
2. Renal excretion of water in response ADH as
stimulated or inhibited by blood smolality
3. Renal Na excretion as blood volume status
Aldosterone
Angiotensin 11
ANP

Hypovolemic hyponatremia
Renal loss (urine Na >20
mmol/day)

Diuretics
Potassium depletion
Aldosterone deficiency
Salt loosing nephropathy

Extra renal loss or cellular shift

(urine Na < 20 mmol/day)

Vomiting
Diarrhea
Fluid loss with burn
Excess sweating
Excess loss with trauma
Potassium depletion

Thirst stimulated by hypovolemia and

result in more hypotonic fluid

Normovolemic hyponatremia
Indicates problem with water balance
1.

SIADH (Syndrome of inappropriate ADH regulation):

Malignancies
Pulmonary disorders
CNS disorders) .

2. Pseudohyponatremia
1.

Sever hyperlipidemia

3. Sever hyperglycemia
4. Excess water intake (polydipsia or chronic thirst)
5. Adrenal insufficiency
1.
2.

Decrease cortisol and aldosterone

decrease level of levels promote ADH secretion and water
retention (restore to normal volume )

Addison,s disesese
Primary adrenal insufficiency:
Addisons disease:
Progressive destruction or dysfunction of
adrenal cortex
Most commonly is of an autoimmune
etiology, resulting from chronic destruction
of the adrenal cortex
All adrenal steroids are deficient

Symptoms of Addisons disease

Fatique
Weakness
GI disturbance
Weight loss
Postprandial hypoglycemia
Dehydration
Hypotension
Hyponatremia
Hyperkalemia
Acidosis
Increased skin pigmentation can be seen with primary adrenal
insufficiency secondary to melanocyte stimulating activity
associated with ACTH

Hypervolemic hyponatremia
Hypervolemic
hyponatremia (urine
Na > 20 mmol/l
Acute or chronic
renal failure

Hypervolemic
hyponatremia (urine
Na < 20 mmol/l
Nephrotic
syndrome
Hepatic cirrhosis
Congestive heart
failure

hypernatremia
Excess water loss ( hypotonic fluid loss)

Renal loss
urine smolality
is N/L (<300)
Diabetes insipidus
Tubular disorders
(acute tubular
necrossis)

Extra renal loss

( urine smolality is
increased)
Insensible loss
(skin & breathing )
Fever
Diarrhea
Burns
Exposure to heat

Decrease water intake

Loss of thirst

Increased Na intake
Or retension
Hypertonic solutions of
Na (Na bicarbonate)
Hypertononc dialysis
solutions
-Problem in neonates
-Hyperaldosteronism

Potassium

Major intracellular cation

20 time greate inside cells than out side cells
Many celular function requires low ECF K level
Only 2% of total K circulate in plasma

Functions of K
Regulation of
Neuromuscular excitability
Elevated K level decreases the resting membrane
potential (RMP) of the cell
Contraction of skeletal and heart muscles
ICF
Hydrogen ion concentration

Regulation of K level
Regulation by the kidney :
All K are reabsorbed in proximal tubules
In the distal tuble: additional K is secreted into urine
in Exchange of Na under the effect of ALDOSTERONE

Distribution of K between cells and ECF

Na/K ATPase pump: K loss if inhibited
Hypoxia
Hypomagnesaemia
Digoxin overload

Insulin : promote entry of K into cells by increasing

Na/K ATPase activity
Epinephrine : promote cellular uptake of K

hypokalemia
GI loss

Vomiting
Diarrhea
Gastric suction
Intestinal
tumors
Malabsorption
Cancer therapy

Renal loss
Diuretics
Nephritis
Renal tubular
acidosis
Hyperaldosteroni
sm
Cushings
syndrome
Hypomagnesaemi
a
Acute leukemia

Cellular
shift
Alkalosis
Insulin
overdose

Symptoms of hypokalemia
< 3mmol/l
Weakness
Fatigue
Constipation
Can lead to paralysis
Increase risk of arrhythmias in pts with heart
disorders

hyperkalemia
Decreased
renal loss
Acute or
chronic RF
hypoaldosteron
ism
Addisons
disease
diuretics

Increased
intake
Oral or IV K
therapy

Artificial :
Sample
haemolysis
Thrombocytosis
Prolonged
torniquate
Drugs:

Cellular shift
Acidosis
Muscle or
cellular injury
Chemotherap
y
Leukemia
Hemolysis
Diabetes
(insulin &
hyperglycemia)

Symptoms of hyperkalemia
Weakness
Tingling
Can lead to paralysis
Increase risk of arrhythmias and cardiac arrest in
pts with heart disorders

specimen for electrolytes

measurement
Serum
Plasma
Lithium
Advantageous for K when platelets counts are elevated

Capillary blood
Heparinized venous or arterial blood
With Direct ISE
Advantageous for K when platelets counts are elevated

Urine:
No addition of preservatives

Na+ and K+ measurement

Specimens: serum, heparnized plasma, whole
blood, sweet, urine, GIT fluids
Methods:
AAS
FES
ISE
spectrophotometery

Flame Emission Spectrophotometry

(Flame photometer)
Sample is diluted with diluents containing
known amount of lithium, as internal
standard , and aspirated into propane air
flame.
Na, K, and Li , when exited, emits light at 589 ,
768 and 671nm , respectively
The emitted lights are selected by interference
filters and read by photodetectors

Flame Emission Spectrophotometry

(Flame photometer)
Na and K can be read at one time from diluted
sample
It is not common in laboratories:
Advances in electrochemistry of ISEs
Needs high amount of maintenance
Safety measures
Electrolyte exclusion effect

Spectrophotometric Methods
Enzymatic methods:
activation of the enzyme beta -galactosidase by
Na to hydrolyze o-nitrophenyl-P-Dgalactopyranoside (ONPG). The rate of
production of o-nitrophenol (the chromophore) is
measured at 420nm

Chemical methods:
Nat or Kt binds to a macrocyclic chromophore
and produce spectral shift color that can be
detected spectrophotometrically.

Spectrophotometric Methods
Not common in laboratories:
High cost of reagents
Easy and availability of ISEs

Ion Selective Electrode

Potentiometric electrode consisting of membrane
selectively permeable to single ion. The potential
produced at membrane sample interface is
proportional to logarithm of the ionic activity or
concentration.
For Na : glass ISE are mostly used
For K : a valinomycin membrane is used to
selectively bind K,
2 types of ISEs
Indirect
direct

Indirect ISE
Sample is diluted with large amount of
diluents before is introduced into the
measurement champer.
Advantage: minimize the effect of proteins in
the electrodes
Most common
Used in automated analyzers
Disadvantage : Electrolyte exclusion effect

Direct ISE
Sample is directly introduced into the measurement
champer without dilution.
Used on blood gas analyzer , POCT devices
Advantage : No electrolyte exclusion effect.
The measure electrolyte activity is directly proportion
to water phase of the plasma (not to the concentration
in the total plasma volume)
Results from direct ISE can be converted to total
plasma volume by using FLAME MODE (mutiply by 0.93)
Considered as method of choice:
Changes in lipid , proteins , other solids common in
deferent pathological conditions dose not affect results

Problems with ISE

Lack of analytical selectivity
Repeated protein coating of ISE membrane
Contamination of membranes with by ions
that

Electrolytes exclusion Effect

Exclusion of the electrolyte from the fraction of
total plasma volume that is occupied by the solids.
Proteins & Lipids ( 7% of plasma volume)
Electrolytes are measure in plasma water fraction
(93%).
Negative error in plasma electrolyte analysis

Mainly problematic in some condition

1. Pathological condition :
Hyperlipidemia
Hyperproteinemia (mutiple myeloma)

2. In methods that needs dilution

FEA
Indirect ISE

Chloride measurement
Major extracelluat anion
Together with Na determine majority of
plasma osmolality.
Osmotic pressure
Maintenance of water balance
Anion cation balance in ECF (electircal
neutrality)

Chloride measurement
Hyperchloremia:
excess loss of HCO3
GIT loss
RTA
Metabolic acidosis

Hypochloremia:

excessive loss of Cl from prolonged vomiting

diabetic ketoacidosis
aldosterone deficiency
Saltlosing renal diseases such as pyelonephritis

Chloride measurement
Specimens: serum, plasma , urine , sweet
Very stable in plasma or serum
No effect of hemolysis

Analytical methods:
Coulometric Amperometric titration
ISE
Reference range :
Serum or plasma: 98 to 107 mmol/l
Spinal fluid : 15% higher than plasma level

Measurement of sweet Cl

To confirm the diagnosis of cystic fibrosis

Most common genetic disorder in caucasians
Newborn screening program
Patients with CF have higher Na and Chloride
Cl- > 60mmol/l : CF presence
Cl- 40 to 60 mmol/ : borderline
Cl- < 40 : exclude CF

Plasma & urine osmolality

Osmosis : the process that constitutes the
movement of solvent across membrane in
response to differences in osmotic pressure
between two sides of the membrane.
Osmometry: Techniques for the measurement
of the solute particles that contributes to the
osmotic pressure. ( Na , Cl, glucose , urea)

Calculation of plasma Osmolality

mOs/kg = = 1.86 (Na[mmol/l])
+ glucose[mmol/l]
+ urea[mmol/l)
+9
Or
mOs/kg = = 1.86 (Na[mmol/l])
+ glucose[mg/dl]/18
+ BUN [mg/dl)/2.8
+9
Reference Range: 275 to 300 mSm/kg

Measurement of smolality
Freezing Point depression osmometer
Vapor pressure osmometer
Osmolal Gap : difference between measured
and calculated smolality
Presence of exogenous osmotic substances
Rule out suspected psedohyponatremia