Hyponatraemia

MMED COURSE July 2021

Dr Rahmah Rasat
UKMSC
Learning Objectives

• Physiology of Na balance
• Evaluation of causes and management of
hyponatraemia
 Content

• Summary of physiology of Na balance

• Pathophysiology of hyponatraemia
• Evaluation of hyponatraemia
• Treatment of hyponatraemic
encephalopathy
• Osmotic demyelination syndrome
• Na-major cation in extracellular fluid (ECF)
• Water shifts-Changes in Na

Total body water (TBW) content

• Newborn- 70 %
• 1 year -60 %
• Na major role on plasma osmolality
TBW- 2/3 intracellular
-1/3 extracellular -plasma, interstitial fluid,
transcellular
Sodium and water balance

• Autonomic NS-renal haemodynamics

-renin secretion
- tubular fluid reabsorption
Changes in Na and H2O balance
Short term regulation -direct via ANS
Long-term regulation-Hormones(ADH,
aldostrerone)
Sodium and water balance

• Kidney -regulates Na absorption to maintain

volume)
-reabsorb Na in response to renal
perfusion
• Hyperosmolality
ADH-aquaporin channel_H2O absorption
- increase nos. epithelial Na receptors -
absorb Na- water retention
• Hypoosmolality
• Osmotic and non-osmotic stimuli-THIRST
✓ Baroceptors(effective intravascular volume)
✓ -high pressure (aorta & carotid sinus)
-Low pressure(atria & great veins)
Arterial underfilling- Increase in ADH
-activation RAAS
-vasoconstriction
- Increase heart rate
- inhibit atrial natriuretic peptides
ENHANCED NA reabsorption and water retention
Low pressure receptors -mechanical stretch in
atria and great veins
Juxtaglomerular apparatus
1.Juxtaglomerular cells-modified smooth
muscle cells of afferent arterioles , secrete
renin
2. Macula densa of distal convoluted
tubule-sense tubular filtrate flow & Na
3. Juxtaglomerular/extra glomerular
mesangial cells ? function
 REGIULATION OF NA AND WATER BALANCE
Hypotension
Decreased blood volume
Sympathetic nerve activation Na & water
Decrease Na delivery to DT reabsorption
Reduced ANG II , ANP

Angiotensinogen
renin
Aldosterone
Angiotensin I

Vasoconstriction
Increased systemic vascular R
ACE Increased BP
Increased cardiac output

Angiotensin II

ADH
Peptide hormones

• ANP
• BNP
-heart
• INCREASE due to increase body fluid
volume
• Actions- vasodilation
- natriuresis
- diuresis
- suppress aldosterone & ADH
Definition

• Serum Na <135 mmol/L

• Na major role in plasma osmolality (285-
295)
• signs , symptoms and complications of
hyponatraemia-due to changes in plasma
osmolality
• 50 % children symptomatic Na<125
mmol/L
Pathophysiology of hyponatraemia

CNS
• Acute (within hours)
Change is osmolality influx of water -
cerebral oedema
• Slow (days)
Brain adaptive response to protect from
oedema
Mechanisms of cerebral oedema

• Na-K ATP ase system

• Aquaporin channels
• Organic osmoles

• Hyponatraemia -reduced osmolarity -influx

of water into brain to glial cells (via water
channel aquaporin (AQP)
• water shunted to astrocytes which swell
• Na extrusion using Na-K ATP ase system
• K ions extrusion follows Na but slower
• Inorganic osmolytes , organic osmolytes
(glycine, taurine, creatine etc) efflux from
cells in hypo-osmolar states in animal
studies)
• Brain’s adaptive response to protect itself
from oedema-takes several days
• Correction of hypo-osmolar extracellular
space to euvolaemic/hypervolaemic state

Rapid Efflux of H2O from brain tissue

Dehydration of brain cells

Osmotic demyelination syndrome

Risk factors for hyponatraemic
encephalopathy/1
1. Age
Prepubescent children increased risk
because brain-to-cranial vault ratio
Brain reach adult size by 6 years but skull by
16 years
Children develop symptomatic
hyponatraemia at relatively higher Na
compared adults
Risk factors for hyponatraemic
encephalopathy/2

2. Sex
Higher in menstruating females
Mortality/permanent neurologic damage-30
X greater> female
Oestrogen implicated? mechanism(?
inhibition of Na-K ATP ase system)
Risk factors for hyponatraemic
encephalopathy/3
3. Hypoxia
2 mechanisms
Hypercapnic respiratory failure due to
central respiratory depression(sign of
impending herniation
Non-cardiogenic pulmonary oedema
Increased ICP-increased vascular
permeability & catecholamine release
Risk factors for hyponatraemic
encephalopathy/3
Effect of hypoxia
• Impair brain adaptive response (active Na
transport & astrocyte volume regulation are
ENERGY dependent process reqd O2)
➢ HYPOXIA-increase cerebral blood flow
a) increase O2 delivery
b) increase cerebral blood volume

INCREASE ICP (worsen outcome)

 Risk factors for hyponatraemic
encephalopathy/4

Vasopressin
1) Decrease cerebral bloodflow (vasoconstriction)
Decrease O2 delivery
Impairs brain adaption
2) Fascilitates direct H2O movement into brain cells
3) Affects energy -dependent process in brain
adaptation
Cardiovascular response to
hyponatraemia
• Intravascular volume
Distribution of water & solutes in
extracellular and Intracellular space
Fluid shifts from extracellular TO intracellular
space - DECREASE arterial blood volume
Haemodynaemic disturbance more
pronounced for degree of dehydration
• Hyponatraemia < 135 mmol/L often due to
+ excess of free water(appropriate ) or
inappropriate ADH (SIADH)
+ Sodium wasting
AETIOLOGY/1

• Hypervolaemic hyponatraemia(excess
free water)
• Hypovolaemic hyponatraemia
Renal loss of Na
Extrarenal loss of Na
• Normovolaemic hyponatraemia
AETIOLOGY/1

Hypervolaemia hyponatraemia
• Congestive heart failure
• Cirrhosis
• Nephrotic syndrome
• Acute or chronic renal failure
AETIOLOGY/2

• Hypovolaemic hyponatraemia
(renal loss of Na in excess of free water)
Diuretic excess
Osmotic excess
Salt-wasting diuresis
Adrenal insufficiency
Pseudohypoaldosteronism
AETIOLOGY/3

Hypovolaemic hyponatraemia due

extrarenal loss of Na in excess of free
water
• GIT-vomiting, diarrhoea, fistulas, drains
• Cystic fibrosis
• Sweat
• Cerebral salt-wasting (CSWS)
• Third -space loss-pancreatitis, burns,
peritonitis, acsites, effusions, muscle
trauma
AETIOLOGY/4

Normovolaemic hyponatraemia (SIADH)

• chest disorders-infection ( TB bacterial,
mycoplasama, viral, fungal)
• Positive pressure ventilation
• CNS-infection (TB, bacteria, encephalitis)
Trauma, Brain tumour)
• Drugs(carbamazepine)
AETIOLOGY/5

Normovolaemic hyponatraemia
• Reset osmostat
• Glucocorticoid deficiency
• Hypothyroidism
• Water intoxication (IV therapy,
psychogenic water drinking)
HISTORY/1

• Hypotonic fluid use for maintenance in

hospitalised patients
• Feeding hypotonic formula during infancy
• Conditions GIT-diarrhoea, vomiting,
fistulas)
• Renal disorders_salt wasting nephropathy,
acute renal failure, chronic renal failure)
• Post-operative states
HISTORY/2

• CNS and pulmonary disease

• Hypothyroidism
• Adrenal insufficiency
• CCF
• Cirrhosis
• Cystic fibrosis
• Drugs(carbamazepine)
 SIGNS/SYMPTOMS

Early Advanced CNS

Anorexia Bizzare behaviour
Nausea Hallucinations
Emesis Obtundation
Headache Incontinence
Impaired response to verbal stimuli
Impaired response to painful stimuli
Seizure
Respiratory insufficiency
Far Advanced CNS signs

• Decorticate/decerebrate posturing
• Bradycardia
• Hypertension/ hypotension
• Altered temperature regulation
• Dilated pupils
• Respiratory arrest
• Coma
Other systems

• CVS
Hypotension
Tachycardia

• Musculoskeletal
Weakness
Muscular cramps
INVESTIGATIONS

• Evaluate serum osmolality

• Normal 285-295 mOSM/kg
• Serum osmolality= 2XNa+ K glucose+urea
 Na < 135 mmol/L

Plasma osmolality

High > 300 NORMAL

Low <285
Translocational 285-295
Hypoosmolar
Hyponatraemia Pseudohyponatraemia
Hyponatraemia
TG, Chol, Protein
Hypertonic hyponatraemic

• Glucose, mannitol, IV radiocontrast, low

molecular weight dextrans

FORMULA in hyperglycaemic states

• Corrected Na =measured Na+(2.4 X
serum glucose -5.5)/ 5.5
 LOW < 285 mmol/L
Hypoosmolar hyponatraemia

Hypovolaemia Euvolaemia Hypervolaemia

FeNa FeNa Fe Na
FeNa <0.5 % FeNa > 0.5 % >0.5% <0.5 % >0.5%.
Extrarenal Diuretic Water Oedematous Acute
salt loss excess intoxication states kidney
vomiting Salt wasting SIADH Nephrotic injury
diarrhoea nephropathy Glucocorticoid synd Chronic
burns Mineralocortic deficiency cirrhosis kidney
peritonitis oid def Hypothyroidis Heart failure diseases
pancreatitis RSWS m
Excess
sweating
CLINICAL MANIFESTATIONS

Asymtomatic Severe neurologic

Dysfunction
CNS symptoms *
CVS
Musculo skeletal
Factors contributing to CNS symptoms
1) Rate of Na change
2) Absolute Na level
3) Duration of abnormal Na level
4) Prescence of other CNS pathology risk
factors
5) Prescence of excessive ADH levels
Treatment

• Systemic dehydration and hypovolaemia :

rehydrated with salt-containing fluids
• Decrease effective plasma volume eg
cardiac failure: treat primary disorder,
water and salt restriction
• Ongoing salt loss : IV & oral sodium
chloride supplementation
Treatment of SIAD

• Chronic SIAD : fluid restriction : 1L/m2/day

• Acute treatment of hyponatraemia if
cerebral dysfunction present
Emergency treatment of hyponatraemia

• Hyponatraemia mostly gradual

• Acute hyponatraemia or Na < 120 mmol/L
--- symptoms: lethargy, psychosis, coma,
seizures---- hyponatraemic
encephalopathy

Hyponatraemia—hypoosmolality ---
intracellular cerebral oedema ---increased
ICP—brain ischaemia---herniation---death
Clinical symptoms of hyponatraemic
encephalopathy
1. Early 2. Advanced
▪ Headache ` seizures
▪ Nausea & Vomiting coma
▪ Lethargy apnoea
Weakness pulmonary oedema
Confusion decorticate posturing
Altered consciousness dilated pupils
Agitation anisocoria
Gait disturbances papilledema
cardiac arrhythmias
myocardial ischaemia
Central diabetes insipidus
Treatment symptomatic of
hyponatraemia
• 2 ml/kg bolus of 3% NaCl (Na =514
mmol/L)over 10 mins. Max 100ml
• Repeat bolus 1-2 X as needed until
symptoms improve.
• Goal:Not more than 2mmol /L/H increase
in serum Na in first 3-4 H
• Recheck SNa following 2nd bolus or Q 2 H
• Hyponatraemic encephalopathy unlikely if
no clinical improvement following an acute
rise in serum sodium
5. Stop further therapy with 3% NaCl boluses
when patients is either :
a. Symptom free: awake, alert, responding to
commands, resolution of headache and
nausea
b. or Na > 125 mmol/L? FOLLOWED by
6. Slow Correction over 48 H SHOULD:
a. Not exceed 12 mmol/L in 24 hours
b. Avoid hypernatraemia

*Limits of rate of correction - 6-15 mmol/L/24

hour-15-20 mmol/L /48 hour
Cerebral demyelination

• Overcorrection of hyponatraemia
• Chronic hyponatraemia(>48 H)
• Additional risk factors!
Risk factors for cerebral demylination in hyponatraemic
patients
1.Severe chronic hyponatraemia :Na < 115 mmol/L
2. Development of hypernatraemia
3. Increase in serum Na > 25 mmol/L in 24 H
4. Hypoxaemia
5. Severe liver disease
6.Thiazide diuretics
7. Alcoholism
8. Cancer
9. Severe burns
10. Malnutrition
11. Hypokalaemia
12. Diabetes
13. Renal failure
OSMOTIC DEMYELINATION
SYNDROME
Uncommon
1960-2018- total of 106 cases
Highest prevalence
1-5 years 35%
Infants 7.5%
M: F =1:1
Manifestatios of ODS

• Asmptomatic
• 2-7 days after correction of hyponatraemia
• Dysarthria
• Spastic quadriplegia
• Pseudobulbar palsy
• Ataxia
• Lock-in state
OSMOTIC DEMYELINATION SYNDROME

Outcome
%
Complete recovery 38
Partial 22
Died 39
After year 2000 (45 subjects)
Recovery 60
Partial 31
Died 9
Factors inffluencing outcome

• ODS occurs with Rapid Na correction

mostly seen in cases with chronic
hyponatraemia
• Acute hyponatraemia of few hours ( eg.
marathon runners)rapid Na correction
usually does not induce ODS
Treatment of osmotic demyelination
syndrome
• General supportive care
• Steroids (prednisolone, dexametasone,
methyprednisolone )
• IV immunoglobulins
➢Recognise hyponatraemia early
➢Differentiate acute versus chronic
hyponatraemia
➢Correctly diagnose volume state of patient
➢Slow correction of hyponatraemia
➢Prevent hyponatraemia in hospitalised
patients with isotonic saline as standard
fluid of choice