WATER & ELECTROLYTE IMBALANCE

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)
ICF

ECF : interstitial space, 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 semipermeable 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
complexed in bone 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 Increased ADH water retention

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

True Na 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 losss

1. Renal loss (urine Na >30 mmol/l )

Diuretics Salt-wasting nephropathy Cerebral salt wasting Mineralocorticoid deficiency (Addisons disease)

2. Extra-renal loss (urine Na < 30 mmol/l)

Skin losses : burns, massively increased sweating Gastrointestinal losses: vomiting, diarrhoea, fistulae

Pathophysiology of hyponatraemia in severe Na depletion

Severe Na depletion

Severe ECV volume depletion (severe hypovolaemia) GFR urine volume aldosterone secretion stimulates renal Na reabsorption in DCT H2O retention ADH secretion stimulates H2O reabsorption via renal collecting ducts

Plasma volume maintained at expense of plasma osmolality

Hyponatraemia

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

Gives rise to dilutional hyponatraemia with

plasma osmolality
Due to :
acute H2O load
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 :
Hyponatraemia : < 135mmol/ Low plasma osmolality : < 285 mmol/kg Natriuresis : urine sodium > 18 mmol/L Inappropriately concentrated urine: urine osmolality >

serum osmolality Normal thyroid, adrenal, renal & liver function 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
nephrotic syndrome

Oedematous states

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 H2O depletion (euvolaemia) Renal loss + inadequate intake
Diabetes insipidus nephrogenic, cranial

Extra-renal loss

N loss with adequate H2O intake

- e.g. 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, hypertonic saline Salt ingestion (excess) Mineralocorticoid excess syndrome + H2O intake

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:
Aldosterone

Excretes K and reabsorbs Na and HCO3 in the distal tubules 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 Transcellular shifts Insulin, catecholamines causes K to shift into cells 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 (Conns

syndrome), Cushings syndrome, exogenous steroids, 2o hyperaldosteronism, carbenoxolone, liquorice ingestion Renal tubular acidosis Ureteral diversions (K and HCO3 is secreted by the colon) Carbonic anhydrase inhibitor (acetazolamide)

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 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

Acute renal failure, CRF, K-sparing diuretics (amiloride, spironolactone, triamterent), mineralocorticoid deficiency (Addisions 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) Addisons disease

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