Significance of Na+, K+ and Cl- investigation
MUDr. Miroslava Hlaváčová, PhD.
Department of biochemistry
Faculty of Medicine, Masaryk University

Sodium cation



Sodium balance and distribution
Na+ concentration in plasma
135 - 145 mmol/L
Na+ concentration in cell
3 - 10 mmol/L
Na+ intake
140 - 260 mmol/day
(8 - 15 g NaCl)
Na+ renal excretion
120 - 240 mmol/day
Na+ excretion via GIT
10 mmol/day
Na+ excretion via sweat
10 - 80 mmol/day
Na+ total excretion
140 - 260 mmol/day
The concentration gradient between ECF and ICF is maintained principally by the Na+/K+ pump.

Assessment of plasma concentration
•anamnesis, clinical symptoms
•S-osmolality:  2x[Na +] + [glucose] + [urea]   (ca. 285 mmol/kg)
•Tonicity : 2x[Na+] + [glucose]
•Evaluation of extracellular volume (dehydration, euvolemia, edema)
•S – albumin
•U - Na +
ØADH:  water reabsorption (distal convoluted tubule)
Øaldosterone: reabsorption of Na+  (+ H₂O) and excretion of K +,H +
Øatrial natriuretic peptide: excretion of Na+ (and water)

Definitions of plasma sodium imbalance
•hyponatremia – the Na+ concentration in the serum is below the physiological range
–mild  130 - 135mmol/L
–moderate 120 - 130 mmol/L
–severe < 120 mmol/L
•acute – last less than 48 hours or the increase in plasma concentration is higher than 0.5
mmol/L/h
•chronic - last more than 48 hours or the increase in plasma concentration is lower than 0.5
mmol/L/h
–TIME DIVISION IS NECESSARY FOR THE SPEED OF THERAPY!
–
•hypernatremia – the Na+ concentration in the serum is above the physiological range, severe above
the 155 mmol/L

•one of the most common electrolyte imbalance
•symptoms depend on the severity of hyponatremia and the speed of development
•symptomatic hyponatremia – 33% mortality or permanent brain damage, in chronic form 25%
Hyponatremia

Symptoms of hyponatremia
•brain edema, increased intracranial pressure, myelinolysis, nausea or vomiting, lung edema with
hypoxia
•no signs if the development of hyponatremia is slow
•beware kids and older people – weaker symptoms even in severe hyponatremia
•risk factors: hypoxemia (vicious circle), female sex (estrogens), alcoholism, hepatopathy , et al.

Hyponatremic encefalopathy
•hyponatremia in ECF
•↓
•movement of water into cells including brain cells
•↓
•brain edema
•↓
•compensational mechanisms decrease the osmolality of ICF (24 – 48 hours)
•↓
•reduction of brain edema
beware of quick therapy!!

Hyponatremic encefalopathy II.
•quick increase of plasma concentration (e.g., rapid correction of hyponatremia)
•↓
•plasma becomes relatively more osmotic compared to ICF
•↓
•movement of water from ICF back to ECF
•↓
•dehydration of brain cells
•↓
•syndrome of central pontine and extrapontine myelinolysis (osmotic demyelination syndrome)

Isoosmolar /
Isotonic
Hyperosmolar /
Hypertonic
Hypoosmolar /
Hypotonic
Osmolality = 2[Na +] + [glucose] + [urea]
pseudohyponatremia (interference of lipids and proteins using some types measurement)
Hyperglycemia
Mannitol
Ethylene glycol
low ECF volume (hypovolemic)
increased ECF volume (hypervolemic)
normal ECF volume (euvolemic / isovolemic)
90%
Types of hyponatremia

Hyperosmolar hyponatremia
•every increase in plasma glucose concentration by 5 mmol/L above the physiological range decreases
the plasma sodium concentration by approx. 1.5 mmol/L
•
§correction formula:
–PNax = PNa+ / (1- PGlc * f)
–
–f = 0,002
–PNax  corrected plasma sodium concentration
–PNa+ measured plasma sodium concentration
–PGlc  measured plasma glucose concentration




Hypoosmolar hyponatremia
[Na +]
hypovolemic
hypervolemic
euvolemic
•relative imbalance between the volume of ECF and the amount of sodium cations included

Hypovolemic hypoosmolar hyponatremia
•Na+ loss is higher than loss of free water (volume of ECF is reduced)
•Extrarenal loss
diarrhea, vomiting, burns
third spacing of fluid (ileus, peritonitis, fistulas, burns, etc.)
•Renal loss
diuretics
aldosterone deficiency
•Signs
Dehydration, risk of kidney failure and blood circulation
•Therapy
isotonic saline
ICF
ECF

Hypervolemic hypoosmolar hyponatremia
•retention of water of hypoosmotic fluid
•Nonrenal causes
cirrhosis, heart failure, nephrotic syndrome with the development of edema (hypoalbuminemia)
•Renal causes
acute renal failure
•Signs
edemas, gain of weight
•Therapy
fluid restriction, water restriction, diuretics
ICF
ECF

Isovolemic hypoosmolar hyponatremia
•retention of pure water with later redistribution into intracellular space
•Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
brain trauma, pneumonia, lung cancer
drugs – carbamazepine, barbiturates, hydrochlorothiazide
•Therapy
water intake restriction, antagonists of ADH receptors
ICF
ECF

Basic notes to therapy
•it is important to:
– judge the severity of hyponatremia, time course of sodium levels and cause of hyponatremia
–assess the ECF volume and osmolality
•treat the cause of hyponatremia if possible
•consider the correction (max. 8 – 12 mmol/L/ 24h in symptomatic patients, in asymptomatic even
slower)
•monitor the level of plasma sodium concentration hourly

Calculation of sodium deficit
•deficit Na+ = m (in kg) * F * (140 – measured plasma Na+ concentration)
•(F = 0.6 for men a 0.55 for women)
•
•target value of plasma sodium concentration: half of the distance between measured value of plasma
sodium concentration and value 140 mmol/L
•
•deficit Na+ target  = m (in kg) * F * (target value of plasma sodium concentration - measured
plasma Na+)

•most common cause of increased osmolality
•very often caused by water deficit rather than sodium cation excess
•hyperosmolality cause the movement of water from ICF to ECF with dehydration of (brain) cells
•compensational mechanism is the increase of solute particles in brain cells
•rapid therapy cause brain edema
Hypernatremia

Signs of hypernatremia
•mostly neurological – because of the water movement in brain cells
§thirst
§irritability, spasticity, aggressivity, insomnia, hyperventilation, coma   → death
§intracranial bleeding (volume changes of brain tissue)
•

category
example
decreased body sodium
(loss of water > Na+)
extrarenal: sweating, diarrhea
renal: osmotic diuresis (diabetes mellitus)
normal body sodium
(loss of pure water)
extrarenal: fever
renal: diabetes insipidus
increased body sodium
(retention of Na+ > water)
steroid treatment, Cushing‘s syndrome, increase intake of sodium (iatrogenic application of
hyperosmolar saline, provoking of vomiting by salt solution, castaways adrift at sea)
Causes of hypernatremia

Therapy of hypernatremia
•the same rules as in therapy of hyponatremia (cause, severity, time course) •typical treatment is
rehydration, oral or intravenous (combination of 5% glucose and saline according to estimated loss
of water and sodium) or diuretics (in case of retention of water and Na+)

Potassium cation



Potassium balance and distribution
K+ is the main intracellular cation – at least 95% of the body's potassium is found inside the
cells
K+ concentration in plasma
3.8 – 5.2 mmol/l
K+ concentration in cell
100 - 160 mmol/l
K+ concentration in urine
30 - 80 mmol/l
intracellular reserve
3200 mmol
extracelullular reserve
60 mmol
K+ intake
50 - 100 mmol/24 h.
K+ excretion
50 - 100 mmol/24 h.

Plasma potassium concentration and pH
•they are dependent (decrease of pH by 0.1 increase plasma potassium concentration by approx. 0.6
mmol/L)
•more accurate is Kazda's formula :
•
•Plasma potassium concentration = 33,05 – 3,87*plasma pH
•
•pH = 7 matches the plasma potassium concentration 6 mmol/L and pH = 7.7 matches the plasma
potassium concentration 3.3 mmol/L
•
•AND IF THE VALUES DO NOT MATCH EACH OTHER?
•

Definitions of plasma potassium imbalance
•hypokalemia – the plasma K+ concentration is below the physiological range
–mild  3.0 – 3.5 mmol/L
–moderate 2.5 – 3.0 mmol/L
–severe < 2.5 mmol/L
–
•hyperkalemia – the K+ concentration in the serum is above the physiological range
–mild  5.5 – 6.5 mmol/L
–moderate 6.5 – 7.5 mmol/L
–severe > 7.5 mmol/L
•

Altered internal distribution
Altered external balance
Other
deficient intake of K+
excessive losses of K+
artefact (collection of blood from a vein near to site of IV infusion)
Types of hypokalemia
Hypokalemia must not be equated with depletion of body K+. Although most patients with K+ depletion
have hypokalemia, acute changes in the distribution of K+ in the body can offset any effects of
depletion or excess.

Hypokalemia due to altered internal distribution of K+
•altered internal distribution = shift of K+ into cells
•
Øalkalosis
Ø
Øinsulin (beware of hypokalemia after starting the treatment of diabetic ketoacidosis)
Ø
Øadrenaline (e.g. after MI)
Ø
Øcellular incorporation of K+ (parenteral re-feeding, rapidly proliferating leukemic cells)

Hypokalemia due tu altered external balance
•deficient intake of K+
Øchronic and severe malnutrition, anorexia nervosa
Ø
•excessive losses of K+ from the renal tract
–
Øhyperaldosteronism, diuretic therapy, renal tubular acidosis, Bartter‘s syndrome
Ø
•excessive losses of K+ from the GI tract
Øvomiting, diarrhea or laxative abuse, fistula
•
Ø
Ø

Signs of hypokalemia
•muscle weakness, spasms
•disturbances of cardiac conduction
•constipation or paralytic ileus
•disturbed concentration of urine and polyuria
•

Principles of therapy
•measure the plasma magnesium concentration – it is necessary for activity of Na+/K+ ATPase
•calculate the deficit of potassium
• K deficit (in mmol)=(K normal lower limit  - K measured) x body weight (kg) x 0.4
•
•correction depends strongly on the kidney function
•IV administration is recommended in severe hypokalemia or if the plasma potassium level is not
responding to oral administration
•maximal dose is 10 - 20 mmol/L/h
•7.5% KCl contents 1mmol/L of K+ in 1 ml
•check the plasma potassium concentration hourly

Altered internal distribution
Altered external balance
Other
increased intake of K+
decreased losses of K+
pseudohyperkalemia
Types of hyperkalemia

Causes of hyperkalemia
•altered internal distribution
–acidosis, uncontrolled diabetes mellitus (lack of insulin), cellular necrosis
•increased intake
–rare, only in combination with renal insufficiency
•decreased excretion
–renal diseases, mineralocorticoid deficiency

Pseudohyperkalemia
•increased amount of potassium in plasma that occurs due to excessive leakage of K+ from cells
during or after blood is drawn
–excessive use of tourniquet
–lack in processing the blood after the collection
–hemolysis
–leukocytosis (> 50 · 109/l)
–trombocytosis (> 750-1000 · 109/l)
•

Principles of therapy
•increase of shift of K+ into cells (glucose + insulin, alkalization, correction of hyponatremia)
•diuretics in nonrenal causes
•calcium gluconate (counter the neuromuscular effect of hyperkalemia)
•renal dialysis in severe hyperkalemia

Practical notes to therapy
•plasma potassium concentration must be judged together with clinical condition of patients (ECG!),
acid – base balance, renal functions and possible K+ depletion
•hypokalemia with acidosis and hyperkalemia with alkalosis are potentially critical
•hypokalemia with increased potassium in urine is usually caused by renal disorder, hypokalemia
with decreased excretion fraction of potassium has usually extrarenal cause. Conversely in
hyperkalemia.
•therapy of hyperkalemia must be quick with monitoring of electrolyte balance every half an hour.

Chloride anion



Chloride balance and distribution
Cl- concentration in plasma
98-107 mmol/L
Cl- concentration in cell
3 mmol/L
Cl- intake
140-260 mmol /24h
(8-15 g NaCl)
Cl- renally excretion
120-240 mmol / 24h
Cl- excretion via intestines
10 mmol / 24h
Cl- excretion via sweat
10-80 mmol / 24h
Cl- total excretion
140-260 mmol / 24h

Chlorides and acid-base balance
•chlorides are necessary for the calculation of anion gap and unmeasured anions
•
•corrected chlorides – reflect the influence of hydration on plasma chloride concentration (how
would be the plasma chloride concentration if the plasma sodium concentration is 140 mmol/l)
•
• Corrected chlorides = [Cl-] ×(140 ÷[Na+])

Hypochloremia
Øis an electrolyte disturbance in which there is an abnormally low level of the chloride ion in the
blood (< 98 mmol/l)
Øaccompanied by hypochloremic alkalosis, hypokalemia, and usually hyponatremia
      Causes:
ØNonrenal:
Ø loss of GI fluids  – vomiting, fistula in proximal part of GIT
ØRenal:
Øincreased renal excretion of Cl- – polyuric stage of renal failure, a massive treatment with
diuretics
Ø
ØTreatment: correction of the underlying cause, saline, 7.5% KCl if the hypokalemia is also present

Hyperchloremia
Øis an electrolyte disturbance in which there is an abnormally elevated level of the chloride ion
in the blood (> 107 mmol/l)
Ø
Øoften combined with  metabolic acidosis and hypernatremia
Ø
ØCauses: infusion therapy, diarrhea, kidney diseases (e.g. renal tubular acidosis),  overactivity
of the parathyroid glands etc.
Ø
ØTreatment:  correcting the underlying cause, restriction of intake, diuretics (rarely)

Thank you for your attention.
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