OBJECTIVES

1. Water distribution, balance and homeostasis

2. Sodium distribution, balance and homeostasis
3. Causes, pathophysiology and effects of
hypernatraemia & hyponatraemia
4. Definition, causes & clinical features of SIADH
5. Potassium distribution, balance and
homeostasis
6. Causes, pathophysiology & effects of
hyperkalaemia & hypokalaemia
WATER : DISTRIBUTION

 Total body H2O (TBW) accounts for ~ 60% of

body weight in men & 55% in women (d/t
greater fat content)

 ⅔ ICF
 ⅓ ECF : ¾ interstitial space, ¼ plasma (8% of
TBW)

 70kg male adult: 42L TBW, 3.4L plasma

WATER : DISTRIBUTION

 H2O not actively transported in body - freely

permeable through ICF & ECF

 Distribution determined by osmotic contents

of ICF & ECF – change in [solute] of a
compartment induces shift of water to
maintain isotonicity
WATER : BALANCE
WATER HOMEOSTASIS
 Equilibrium between ICF and ECF is reflected in
osmolality of ECF

 Osmolality – the number of osmotically active

particles in a solution

 Normal range of ECF osmolality = 282-295 mmol/kg

of H2O

 Osmolality is altered by changes in body H2O

content independent of [solute]
 Osmosis
 Movement of solvent (water)
from an area of lower solute
concentration to one of higher
concentration
 Occurs through a semi-
permeable membrane using
osmotic pressure (water
pulling)
Mean Arterial Blood
Pressure
 Arterial BP is a reflection of fluid homeostasis
 MABP = Cardiac output (CO) x Total peripheral
Resistance (TPR)
 CO = Heart rate (HR) x Stroke volume (SV)
 By controlling these factors, you can maintain
normal BP therefore normal fluid balance

MABP = HR x SV x TPR
 Regulatory Mechanisms of
Fluid Balance

 Renin-angiotensin-aldosterone mechanism
(RAS)
1. Antidiuretic hormone (ADH/ vasopressin)
 Opens water channels in the renal collecting ducts
 Increase water reabsorption
2. Thirst centre in the hypothalamus of the brain
3. Redistribution of water between ICF and ECF
Renin Angiotensin Aldosterone System
IMPORTANCE OF SODIUM

 Sodium is a positively charged ion (cation)

 It is important because:
 It is a predominant cation in ECF
 It is a main determinant of plasma
osmolality
 ECF volume is determined by total body
Na content
SODIUM: DISTRIBUTION & BALANCE

• Total Na content in normal adult ~ 4000 mmol

 ⅓ complexed in bone
 ⅔ freely exchangeable – majority extracellular
• ECF [Na] ~ 135-145 mmol/L ; ICF [Na] ~ 4-10
mmol/L
• Na intake : 5-500 mmol/day, average western
100-200 mmol/day
• Obligatory Na loss (kidneys, skin, gut) ~ 10
mmol/day
 Excess Na excreted in urine
SODIUM: HOMEOSTASIS
 Massive internal turnover of Na exists
 secreted into gut ~ 1000/day
 filtered by kidneys ~ 25,000/day
 vast majority of Na regained by absorption in gut &
renal tubules
 Sodium balance is maintained by regulation of
its renal excretion via:
 GFR
 renin-angiotensin-aldosterone system (RAAS)
 Natriuretic hormone : atrial natriuretic peptide (ANP)
SODIUM DISORDERS

 Sodium disorders often accompany disorders

of water regulation (too little or too much
water is present )
 Thus, hyponatremia and hypernatremia can
occur with normal, low, or high total body
sodium content, and with euvolemic,
hypervolemic or hypovolemic TBW states
HYPONATRAEMIA

• Plasma [Na] depends on both Na & H2O in

plasma
– thus, ↓ [Na] does not necessarily mean Na depletion

• Hyponatraemia = measured serum sodium < 135

mmol/L
HYPONATRAEMIA: Causes (Clinical)
1) Pseudohyponatraemia (N plasma osmolality)
 hyperlipidaemia, hyperproteinaemia

2) Hypertonic hyponatraemia (↑plasma osmolality)

 hyperglycaemia (e.g. DKA)

3) Hypotonic hyponatraemia (↓ plasma osmolality)

 Hypovolaemia – renal/exra-renal causes
 Euvolaemia – acute/chronic H2O load
 Hypervolaemia –oedematous states
Normal plasma osmolality

Pseudohyponatraemia
 ↓ fraction of H2O content of plasma because
of water displacement (along with Na)

 Due to:
 severe hypertriglyceridaemia
 severe hyperproteinaemia
Increased plasma osmolality

Hypertonic Hyponatraemia
 Addition of a solute to the plasma which is
confined to the ECF causes increased
osmolality leading to:
 water shifting from ICF to ECF by osmosis –
dilutional effect
 Osmotic diuresis – loss of water and Na from
kidneys
 Example :
 Hyperglycaemia
Decreased plasma osmolality

• 3 pathological mechanisms responsible:

1. depletion of Na (hypovolaemic, hyponatraemia)

2. excess of H2O (euvolaemic, hyponatraemia)

3. excess of H2O > Na (hypervolaemic,

hyponatraemia)
(1) Hypovolaemic, Hyponatraemia

 Sodium depletion – rarely d/t inadequate oral

intake alone (inadequate parenteral input is
responsible sometimes)

 Na losses from body is almost always

accompanied by ECF water loss →
hypovolaemia
Causes of excessive Na loss

1. Renal loss (urine Na >20 mmol/l )

 Diuretics (thiazides/ loop diuretics)
 Salt-wasting nephropathy (polycystic kidneys, medullary
cystic kidneys)
 Mineralocorticoid deficiency (Addison’s disease)
 Renal tubular acidosis type II (RTA type II)
 Cerebral salt-wasting
2. Extra-renal loss (urine Na < 10 mmol/l)
 Skin losses : burns, massively increased sweating
 Gastrointestinal losses: vomiting, diarrhoea, fistulae
Clinical effects
 Symptoms
 weakness, apathy, postural dizziness, syncope
 Signs
 weight loss (severe cases)
 CVS( related to ↓plasma vol) – tachycardia, hypotension,
peripheral circulatory failure
 renal – oliguria & concentrated urine
 related to ↓ interstitial fluid - ↓skin turgor, ↓intraocular
pressure
 Biochemistry : ↑ plasma urea & creatinine (↓ GFR)
(2) Euvolaemic,
Hyponatraemia
 Water excess – dilutional hyponatraemia with ↓
plasma osmolality

 Due to :
 acute H2O load – purely excessive fluid intake (rare)
 chronic H2O load
Acute H2O load (urine Na < 20 mmol/L) d/t :
 Excessive H2O intake
 rare because normal kidneys are capable of excreting 1L
of H2O /hr
 psychotics & heavy beer drinkers – large quantities of fluid
ingested rapidly → acute water intoxication &
hyponatraemia
 Excessive hypotonic fluid intake & impairment of
diuresis
 Eg: Excessive iv administration of hypotonic fluids (5%
dextrose or ‘dextrose-saline’) in post-op patient
Chronic H2O load (urine Na > 20 mmol/L) d/t
 persistent natriuresis
 Syndrome of Inapproprite ADH (SIADH)
 hypothyroidism
 hypoadrenalism
 impairment of renal diluting mechanism
 chronic renal failure
Syndrome of Inappropriate ADH
(SIADH)

 Inappropriate release of Antidiuretic hormone,

resulting in fluid retention.
 Diagnostic criteria :
1. Hyponatraemia : < 135mmol/
2. Low plasma osmolality : < 285 mmol/kg
3. Natriuresis : urine sodium > 18 mmol/L
4. Inappropriately concentrated urine: urine osmolality >
serum osmolality
5. Normal thyroid, adrenal, renal & liver function
6. Euvolaemic
SIADH - Causes
 Ectopic secretion of ADH
 Ca bronchus
 Other tumours – Ca thymus, prostate, pancreas

• Inappropriate secretion of ADH

(a)Cerebral diseases:
 Tumours : glioma, meningioma
 Infection : encephalitis, meningitis, abscess
 Trauma : Head injury
 Vascular : CVA, aneurysm, subdural haemorrhage
SIADH - Causes
(b) Pulmonary diseases :
 Infection : TB, pneumonia
 Pneumothorax
 Positive pressure mechanical ventilation

(c) Miscellaneous :
 Pain (post-operative), hypothyroidism
 Drugs – hypnotics (morphine), narcotics(opiates)
hypoglycaemic agents (chlopropamide),
antineoplastics (vinca alkaloids,
cyclophosphamide), anticonvulsants
(carbamazepine)
(3) Hypervolaemic, Hyponatraemia

 Combined H2O & Na excess

 Frequent cause of hyponatraemia

 Causes:
 CHF
 liver cirrhosis Oedematous states
 nephrotic syndrome
Pathogenesis of Oedematous
States
1. Nephrotic syndrome and Liver cirrhosis :
decreased protein – decrease oncotic pressure
2. CHF : sluggish flow – increase hydrostatic
pressure
3. Imbalances of oncotic and hydrostatic pressure
– movement of water into interstium – oedema
4. Effective ECF volume decreases – triggers RAS
5. Secondary hyperaldosteronism
HYPONATRAEMIA -Investigations

 Inspection for lipaemia or proteinaemia

 Serum
 osmolality, glucose, urea, creatinine, potassium,
total protein, TG, fT4/TSH, haematocrit, cortisol

 Urine
 osmolality, sodium
 Hypernatraemia

 Less common than hyponatraemia

 Causes can be divided into:

 pure H2O depletion
 combined Na & H2O depletion (H2O loss > Na loss)
 Na excess -rare
HYPERNATRAEMIA : Causes
(1) Pure water loss (Euvolaemia)
 Renal loss (u osmolality <800mosmol/kg)
 Diabetes insipidus – nephrogenic, cranial

 Extra-renal loss (u osmolality >800mosmol/kg)

 Insensible loss with inadequate H2O intake
 no/poor access to H2O – too young, old, sick to drink,
unable to drink (e.g. obstruction to oesophagus), lesions
to thirst centre
 Fever
 Hyperventilation
(2) Hypotonic fluid loss (hypovolaemia)
 Renal loss + inadequate intake
 Osmotic diuresis – glucose, mannitol, urea

 Extra-renal loss + inadequate intake

 GIT – vomiting, diarrhoea, fistula
 Skin – excessive sweating
(3) Salt gain (hypervolaemia)
 Rare
 Iatrogenic – IV Na bicarbonate
infusion, hypertonic saline infusion
 Excess salt ingestion
 Mineralocorticoid excess (Conn’s
syndrome)
POTASSIUM - Homeostasis
 Healthy kidneys less efficient at conserving K than Na.

 Urinary K excretion remains at 10-20 mmol/24H even on

K free intake.

 Obligatory loss (skin & gut) approx. 15-20 mmol/24H –

kidney cannot compensate if intake is < 40 mmol/24H.

 Average diet contains high amount of K but K depletion

can occur even on a N diet if there is ↑ loss from the
body.
POTASSIUM: Distribution &
balance
 Predominant intracellular cation
 [ICF] = 110 mmol/L, [ECF] = 4 mmol/L
 95% of total = freely exchangeable
 The rest – bound in RBCs, bone, brain
 2% of total – ECF
POTASSIUM - Homeostasis
 Normal range of ECF K : 3.5 -5.0 mmol/L

 ECF K balance is controlled by :

(1) kidneys (primary organ) (2)GIT (less extent)

 These are the following mechanisms of potassium homeostasis:

1. Aldosterone
 Excretes K and reabsorbs Na and HCO3 in the distal tubules
2. Acid-base status
 Acidaemia – K moves out of cells and H+ moves into cells
 Alkalaemia – K moves into cells and H+ moves out of cells
3. Transcellular shifts
 Insulin, catecholamines causes K to shift into cells
4. K secretion in colon
HYPOKALAEMIA - Causes

1. ↓ K intake (urinary [K] < 20 mmol/L)

2. ↑ K loss :
 Renal (urinary [K] > 20 mmol/L)
 Extra-renal (urinary [K] < 20 mmol/L)

3. Transcellular shift (urinary [K] < 20 mmol/L)

HYPOKALAEMIA - Causes
3. ↑ K loss
(a) Renal loss (urinary [K] > 20 mmol/L)
 diuretics
 mineralocorticoid excess – 1o hyperaldosteronism (Conn’s
syndrome), Cushing’s syndrome, exogenous steroids, 2o
hyperaldosteronism, carbenoxolone, liquorice ingestion
 Type I RTA (excessive H+ excretion – increase K loss to
negate Na reabsorption at distal tubules)
 Ureteral diversions (K and HCO3 is secreted by the colon)
HYPOKALAEMIA - Causes

(b) Extra-renal loss (urinary [K] < 20 mmol/L)

 Diarrhoea / purgative abuse
 Villous adenoma of colon
 Enterocutaneous fistula
 Vomiting /gastric aspiration
 Excessive sweating
HYPOKALAEMIA - Causes

1. ↓ K intake
 oral (rare) –chronic alcoholism, anorexia nervosa
 parenteral therapy – inappropriate IV therapy

2. Transcellular shift
 metabolic acidosis
 Insulin administration
 Β adrenergic agonists – salbutamol
HYPOKALAEMIA:
Effects & Complications

 Asymptomatic – even in severe cases

 Disturbances to neuromuscular function
 Muscle weakness (e.g. proximal myopathy)
 Constipation
 Paralytic ileus
HYPOKALAEMIA - Investigations

 Plasma [HCO3]
 Urine [K]
 Serum cortisol – 9am, 12 mn
 Dexamethasone suppresion test
 Renin/aldosterone
 Imaging – USS, CT, MRI
HYPERKALAEMIA - Causes
1. Pseudohyperkalaemia
 haemolysis, delayed separation of serum, contamination,
leucocytosis / thrombocytosis

2. Transcellular shift
 Tissue damage (crush injury, burns, malignancy)
 Acidosis
 Lack of insulin (DKA)
3. ↓ K loss
 ARF, CRF, K-sparing diuretics (amiloride,
spironolactone, triamterent), mineralocorticoid
deficiency (Addision’s disease)

4. Excessive K intake
 oral (rare except with K-sparing diuretics), parenteral
infusion, transfusion of stored blood (contain K citrate
additives)
HYPERKALAEMIA: Effects &
Complications
 Lowers resting membrane potential, shortens
cardiac action potential, increases speed of
repolarisation

 Ventricular fibrillation, cardiac arrest – fatal

 ECG changes : tall T waves, loss of P waves,

abnormal QRS complexes
 HYPERKALAEMIA -
Investigations
Exclude:
 Pseudohyperkalaemia – assess the serum
 ARF – renal profile
 DM – plasma glucose, urine glucose and ketones
 Drugs – ACE inhibitors, K-sparing diuretics

 Serum [HCO3] metabolic acidosis

 Anion gap + high anion gap - DKA, renal failure
 Serum cortisol, ACTH stimulation (Synacthen test) –
Addison’s disease
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