1. Division of Chemical Pathology
David Haarburger

2. Fluid compartments
Human body is approximately 60% water
Total body water 42ℓ
Transcellular fluid (7%) 1ℓ
Plasma (23%) 3ℓ
Interstitial fluid (70%) 10ℓ
Intracellular fluid (⅔) 28ℓ Extracellular fluid (⅓) 14ℓ

3. Composition of body fluids
Extracellular fluid (plasma) Intracellular fluid
Na+ 142 mmol/ℓ Na+ 10 mmol/ℓ
K+ 4 mmol/ℓ K+ 160 mmol/ℓ
Ca2+ 2 mmol/ℓ Ca2+ <0.01 mmol/ℓ
Mg2+ 1 mmol/ℓ Mg2+ 13 mmol/ℓ
Cl- 105 mmol/ℓ Cl- 3 mmol/ℓ
HCO3- 27 mmol/ℓ HCO3- 10 mmol/ℓ
Phosphates 1 mmol/ℓ Phosphates 100 mmol/ℓ
Protein 70 g/ℓ Protein 200 g/ℓ
Osmolarity 290 mosm/ℓ Osmolarity 290 mosm/ℓ

4. Composition of other fluids
Daily production Na+ K+ Cl- HCO3-
(mℓ) (mmol/ℓ) (mmol/ℓ) (mmol/ℓ) (mmol/ℓ)
Saliva 1000 20-80 10-20 20-40 20-60
Gastric 1000-2000 20-100 5-10 120-160 0
Pancreatic 1000 120 5-10 10-60 80-120
Bile 1000 150 5-10 40-80 20-40
Small bowel 2000-5000 140 20 105 25-50
Large bowel 200-1500 80-140 30 30 60
Sweat 200-1000 20-70 5-10 40-60 16

5. Osmotic concentration
The total concentration of
solutes in a solution
Represents the number of
particles
Measured in osmoles per litre
Colligative properties
Lowering of vapour pressure
Elevation of boiling point
Depression of freezing point
Osmotic pressure

6. Plasma osmolarity
Plasma osmolarity Molarity
290 mosmol/ℓ 5 5 4
11
Measured vs Estimated 25
Sodium
Chloride
2x([Na+] + [K+]) + Urea 140
Bicarbonate
Glucose
+ Glucose Urea
Tonicity 100 Potassium
Other
Active osmolyte /
Penetrating solute
Cell

7. Sodium
Primary cation of extracellular fluid
Primary determinant of extracellular
osmolarity
Intimately related to fluid balance
Hypernatraemia causes cerebral
dehydration
Lethargy, weakness, irritability
Twitching, seizures, and coma
Hyponatraemia causes cerebral
oedema
Nausea, malaise, lethargy
Obtundation, seizures, coma

8. Sodium
Hypernatraemia caused by Hyponatraemia caused by
Increased sodium intake Decreased sodium intake
Drinking seawater Increased sodium loss
Intravenous hypertonic Diarrhoea
saline Diuretics
Decreased free water Increased free water
intake intake
Hypodypsia Polydypsia
Increased free water loss Exercise-associated
Sweating, fever hyponatraemia
Diabetes insipidus Decreased free water loss
Osmotic diuresis (glucose, SIADH
mannitol) Advanced renal failure

9. Sodium and water loss
Normonatraemic
hypovolaemia Normal
Loss of sodium and water
Haemorrhage
Burns
Effusion of ECF in body spaces
(ascites) Free
Prone to circulatory collapse water
Hypernatraemic loss
hypovolaemia
Loss of low sodium water
Sweating
Diabetes insipidus
Prone to cerebral Isotonic
dehydration fluid
loss

10. Sodium and fluid homeostasis
Renin-angiotensin-aldosterone system
Low renal perfusion
Increased renin secretion
Angiotensinogen → Angiotensin I
Vasoconstriction
Angiotensin I → Angiotensin II Increased ADH releaseVaso-
constriction
Increased sodium
reabsorption
Increased aldosterone secretion
Increased sodium (water) absorption

11. Sodium and fluid homeostasis
Arginine vasopressin
High osmolarity / Low plasma volume
Increased ADH secretion
Increased thirst
Increased (free) water reabsoption
Vasoconstriction

12. Sodium
Clinical conditions associated with Clinical conditions associated with
hypernatraemia hyponatraemia
Sodium excess Water excess
Inappropriate ADH secretion
High sodium intake Glucocorticoid deficiency
Administration of high sodium Hypothyroidism
containing fluids Psychogenic polydypsia
Condition associated with increased total body sodium
Primary hyperaldosteronsism Heart failure
Water deficiency Liver disease
Renal failure
Burns Nephrotic syndrome
Hyperventilation Sodium deficiency
GIT losses (vomiting, diarrhoea)
Diabetes insipidus Burns
Decreased fluid intake Diuretic therapy
Adrenal insufficiency
Conditions associated with a decreased Salt-losing nephropathy
total body sodium Renal tubular acidosis
Osmotic diuresis Osmotic diuresis
Diabetes mellitus, mannitol infusion Bicarbonaturia, ketonuria
Excessive sweating Transcellular movement
Adrenal insufficiency
Exercise, fever
Sick cell syndrome
GIT losses (vomiting, diarrhoea) Pseudohyponatraemia
Hyperlipidaemia, hyperglobulinaemia

13. Potassium
Predominant intracellular cation
Only 2% of potassium is extracellular [K+] = 4 [K+] = 150
Major role of K+ is to create a membrane K+
potential in excitable cells (nerve, Na+
muscle, β-cells of pancreas)
Plasma potassium negatively regulated
by aldosterone ―
+ CELL
Hypokalaemia hyperpolarises cells -90mV
Muscle weakness
Decreased cardiac excitability, cardiac
arrest
Decreased insulin secretion
Hyperkalaemia depolarises cells voltage-gated
Na channel,
Cardiac arrhythmias, ventricular opens once
fibrillation membrane
potential falls
to -60mV

14. Potassium
Predominant intracellular cation
Only 2% of potassium is extracellular
Plasma potassium is a poor indicator of
body potassium
Major role of K+ is to create a membrane
potential in excitable cells (nerve, muscle,
β-cells of pancreas) Distal convoluted tubule
Hypokalaemia hyperpolarises cells
Muscle weakness
Na+
Decreased cardiac excitability, cardiac ATP
Na+
arrest K+ K+
Decreased insulin secretion
Hyperkalaemia depolarises cells H+
Cardiac arrhythmias, ventricular
fibrillation
Plasma potassium negatively regulated by
aldosterone Tubular
lumen

15. Potassium
Hypokalaemia caused by Hyperkalaemia caused by
Decreased intake Increased intake
Starvation (anorexia Rapid blood transfusion
nervosa) Decreased losses
Increased losses Renal failure
GIT loss (diarrhoea) Aldosterone deficiency
Urine losses (diuretics, (Addison’s disease)
excess aldosterone) Extra-cellular shift
Intra-cellular shift Acute tissue damage
β-Agonists (haemolysis,
Alkalosis, glucose uptake rhabdomyolysis, tumour
lysis)

16. Potassium
Clinical conditions associated with Clinical conditions associated with
hypokalaemia hyperkalaemiea
Potassium deficiency Potassium excess
Low intake Increased intake
Oral potassium supplementation
Alcoholism
Intravenous potassium administration
Anorexia nervosa
Transfusion of aged blood
Increased GIT losses Decreased excretion
Vomiting, diarrhoea, malabsorption Renal failure
Fistulas, laxatives Hypoaldosteronism
Increased urinary losses Diuretics
Amiloride, spironolactone, triamterene
Increased aldosterone
Primary aldosteronism Transcellular shift
Adrenal hyperplasia α-adrenergic stimulation
Androgenital syndrome β-adrenergic blockade
Renal disease Metabolic acidosis
Renal tubular acidosis Crush injuries
Fanconi syndrome Tissue hypoxia
Diuretics Insulin deficiency
Loop diuretics, thiazides, carbonic anhydrase Digitalis overdose
inhibitors
Pseudohyperkalaemia
Transcellular shift Haemolysis
Alkalosis Leukocytosis
Increased plasma insulin

17. Chloride
Primary anion of extracellular fluid
Intimately associated with sodium
No symptoms directly associated to hyperchloraemia
or hypochloraemia
Hyperchloraemia caused by
Causes of hypernatraemia
Metabolic acidosis
Hypochloraemia caused by
Causes of hyponatraemia
Metabolic alkalosis