Importance of metabolites

1. Sodium Metabolism,
Hypernatremia &
Hyponatremia
Dr. Ashik Majumder
Pediatrics

2. • Sodium is the dominant cation of the ECF and it
is the principal determinant of extracellular
osmolality.
• Less than 3% of sodium is intracellular. More
than 40% of total body sodium is in bone; the
remainder is in the interstitial and intravascular
spaces.
• The low intracellular sodium concentration,
approximately 10 mEq/L, is maintained by
Na+K+ATPase, which exchanges intracellular
sodium for extracellular potassium.
• Normal serum sodium concentration varies
between 135 and 145 mEq/l.

3. Electrolyte composition of intracellular
and extracellular fluid compartments

4. Intake & absorption
• Daily sodium requirement is 2 to 3 mEq/kg body
weight although intakes are generally well in
excess
• The requirement varies with age. It is nearly two-
to three-folds higher in term and very low birth
weight preterm babies, a reflection of immaturity
of renal tubular function and higher requirements
for growth
• Adult requirements decrease to 1.5 mEq/kg/ day
• Infants receive sodium from breast milk (≈7
mEq/L) and formula (7-13 mEq/L, for 20
calorie/oz formula)

5. • Absorption of sodium from intestine is via two
mechanisms:
– Freely permeable across the interstitial cell
– Symport with glucose and aminoacids.

6. Excretion
• Sodium excretion occurs in stool and sweat,
but the kidney regulates sodium balance and is
the principal site of sodium excretion
• Normally, sweat has 5-40 mEq/L of sodium.
Sweat sodium concentration is increased in
children with cystic fibrosis, aldosterone
deficiency, or pseudohypoaldosteronism

7. • The regulation of sodium is the major
determinant of sodium balance. Mainly
sodium is reabsorbed at three regions in the
nephrons:
1. PCT- 2/3rd of Na+ reabsorbed
2. TALH- 20-30% is reabsorbed via apical Na+ K+
2Cl- transporter
3. DCT- 5% by thiazide sensitive Na+ Cl-
cotransporter.
4. Final reabsorption also occurs in cortical and
medullary collecting ducts.

8. Overview of Na+ reabsorption along the Nephron

9. • Sodium excretion is regulated at 4 major steps:
1. Circulating levels of aldosterones- it primarily at on
cortical collecting ducts specially T cell to increase
ENaC in apical membrane
2. Circulating number of ANP & othernatriuretic
hormones- ANP causes increase cGMP and this
inhibits transport via ENaC
3. Amount of AT-II, PGE2 levels in kidney- increase
reabsorption of Na+ and HCO3- by action on PCT.
PGE2 causes natriuresis by inhibition of Na+
transport via ENaC
4. Rate of tubular secretion of K+ and H+ - sodium
reabsorption is coupled with H+ and K+ secretion in
tubules and play an important role in acid base
metabolism.

10. Defense of ECF volume and Ionic
composition of the body
Angiotensin 2
Angiotensin 1
Angiotensin
Hypothalamus
ADH
Adrenal
cortex
Renin
Aldosterone
Kidney
Sodium, water
retention
Thirst
Vasoconstriction
Hyperosmolarity
Hypovolemia
ACE

11. Hypernatremia
• Hypernatremia is sodium concentration > 145
mEq/L
• Mild hypernatremia is fairly common in
children especially among infants with
gastroenteritis and in hospitalized patients
which maybe iatrogenic caused by inadequate
water administration or less often by excessive
sodium administration

12. Causes of hypernatremia
• Excessive sodium
– Improperly mixed formula
– Excess sodium bicarbonate
– Ingestion of sea water or sodium chloride
– Intravenous hypertonic saline
– Hyperaldosteronism
• Water deficit
– Nephrogenic diabetes insipidus
– Central diabetic insipidus
– Increased insensible water losses (premature infants,
radian warmers, phototherapy, inadequate intake:
ineffective breast feeding, child neglected, adipsia)

13. • Water and sodium deficit
– Gastrointestinal losses (diarrhea, emesis
/nasogastro suction,osmotic cathartics-lactulose)
– Cuteneous losses (burns, excessive sweating)
– Renal losses (osmotic diauretics-mannitol, diabetes
mallitus, chronic kidney disease, polyuric phase of
ATN, post-obstructive diuresis)

14. Clinical manifestations
• Most children with hypernatremia are
dehydrated
• Breastfed infants with hypernatremia are often
profoundly dehydrated with failure to thrive.
• infant has a “doughy” feel
• Hypernatremia without dehydration causes CNS
symptoms. Patients are irritable, restless, weak
and lethargic. Some infants have high-pitched
cry and hyperpnea , alert patients are very
thirsty.
• Hypernatremia may cause fever

15. • Brain haemorrage is the most devastating
consequence of untreated hypernatremia. Patients
may have subarachnoid, subdural, and
parenchyma haemorrages. Seizures and coma are
possible sequelae of haemorrages.
• Cerebral pontine myelinolysis (CPM) and extra
pontine myelinolysis can occur in children with
hypernatremia. CPM is classically associated with
overly rapid correction of hyponatremia.
• Thrombotic complications occur in severe
hypernatremic dehydration include stroke, dural
sinus thrombosis, peripheral thrombosis and renal
vein thrombosis (secondary to dehydration and
hypercoagulability).

16. Diagnosis

17. Treatment
• Hypernatremia should not be corrected rapidly
• The goal is to decrease the serum sodium by <12 mEq/L
every 24 hr, a rate of 0.5 mEq/L/hr
• If a child has seizures as a result of brain edema secondary
to rapid correction, administration of hypotonic fluid
should be stopped. An infusion of 3% saline can acutely
increase the serum sodium to reversing the cerebral edema
• In a child with hypernatremic dehydration, the first
priority is restoration of intravascular volume with
isotonic solution. Normal saline is preferable to RL.
Repeated boluses of NS (10-20ml/kg) may be required to
treat hypotension, tachycardia and signs of poor perfusion

18. • Correction of water deficit: calculate water deficit as
below
water deficit = body weight x 0.6(1-145)/ current sodium
Administer half-normal saline (0.45%) or oral water
to replace the ongoing losses. If signs and symptoms of
volume depletion develop the patient receives
additional boluses of isotonic saline
• Acute severe hypernatremia, usually secondary to
sodium administration can be corrected more rapidly
• When hypernatremia is severe and is caused by sodium
intoxication it maybe impossible to administer enough
water to correct hypernatremia rapidly, in this situation
dialysis can be done to remove the excess sodium
• In less severe cases, addition of loop diuretic increases
removal of excess sodium and water decreasing the risk
of volume overload

19. • With sodium overload, hypernatremia can also
be corrected with sodium free intravenous
fluid (5% dextrose in water)
• In case of a child with central diabetes
insipidus, patient should receive desmopressin
acetate 5-40mg once or twice daily intranasal
or oral start with 0.05mg/dose BD gradually
increase to 0.8mg/day.
• Over the long-term, reduced sodium intake.
• Patients with significant ongoing losses, such
as through diarrhea, may need supplemental
water and electrolytes.

20. Hyponatremia
• Hyponatremia is a serum sodium level <135
mEq/L.
• Hyponatremia exists when the ratio of water to
sodium is increased.
• This condition can occur with low, normal or
high levels of body sodium. Similarly, body
water can be low, normal or high.

21. Causes of Hyponatremia
• Pseudohyponatremia
• Hyperlipidemia
• Hyperproteinemia
• Hyperosmolality
• Hyperglycemia
• Iatrogenic (mannitol, sucrose, glycine)
• Hypovolemic hyponatremia
– Extrarenal losses
• Gastrointestinal (emesis, diarrhea)
• Skin (sweating or burns)
• Third space losses (bowel obstruction, peritonitis,
sepsis)

22. – Renal losses
• Thiazide or loop diuretics
• Osmotic diuresis
• Postobstructive diuresis
• Polyuric phase of ATN
• Juvenile nephronophthisis
• Autosomal recessive polycystic kidney disease
• Tubulointerstitial nephritis
• Obstructive uropathy
• Cerebral salt wasting
• Proximal (typeII) renal tubular acidosis
• Lack of aldosterone effect (high serum potassium):
absence of aldosterone e.g. 21-hydroxylase
deficiency, pseudohypoaldosterone type I, urinary
tract obstruction and infection

23. • Euvolemic hyponatremia
• Syndrome of inappropriate antidiuretic hormone
syndrome (SIADH)
• Nephrogenic syndrome of inappropriate
antidiuresis
• Desmopressin acetate
• Glucocorticoid deficiency
• Hypothyroidism
• Water intoxication: iatrogenic (excess hypotonic
intravenous fluids), feeding infants excessive
water products, swimming lessons, tap water
enema, psychogenic polydipsia, diluted formula.

24. • Hypervolemia hyponatremia
• Heart failure
• Cirrhosis
• Nephrotic syndrome
• Acute, chronic kidney injury
• Capillary leak caused by sepsis
• Hypoalbuminemia caused by gastrointestinal
disease (protein-losing enteropathy).

25. Clinical manifestations
• Majority of patients have no symptoms, symptoms
often develop in patients with serum sodium
concentration <125mEq/L or in whom the sodium has
decreased rapidly
• Increase intracranial pressure which impairs cerebral
blood flow and in acute severe hyponatremia it can
cause brainstem herniation and apnea
• Neurological symptoms include anorexia, nausea,
emesis, malaise, lethargy, confusion, agitation,
headache, seizures, coma, and decreased reflexes
• Patient may have cheyne-stokes breathing
• Hyponatremia can cause muscle cramps and weakness;
rhabdomyolysis can occur with water intoxication

26. Diagnosis

27. Treatment
• The management requires judicious monitoring and
avoidance of an overly quick normalization of serum
sodium concentration. But in case of patient with
severe symptoms (seizures) a bolus of hypertonic saline
should be given to produce a small, rapid increase in
serum sodium.
• Hyponatremia can cause hypoxia and hypoxia worsens
cerebral edema, hence, pulse oximetry should be
monitored and hypoxia aggressively corrected.
• In all cases of hyponatremia it is important to avoid
rapid correction, which may cause CPM . It is advisable
to avoid correcting the serum sodium concentration by
>12mEq/L/24hr or >18mEq/L/48 hr

28. • In hypovolemic hyponatremia the patient has a deficiency
deficit in sodium and may have a deficiency in water. So
the first step in treating any dehydrated patient is to restore
the intravascular volume with isotonic solution.
• In hypervolemic hyponatremia the patient have an excess
of both water and sodium. The cornerstone of therapy is
water and sodium restriction because the patient have
volume overload. Diuretics may be used, as it will cause
excretion of both sodium and water. Vasopressin
antagonists are effective in correcting the hypervalemic
hyponatremia caused by heart failure or cirrhosis.
• Children with iatrogenic hyponatremia caused by
administration of hypotonic IV should received 3% saline
if symptomatic.

29. • Specific hormone replacement therapy for
hyponatremia of hypothyroidism or cortisol
deficiency.
• SIADH is a condition of excess water with
limited ability of kidney to excrete water, the
mainstay of its therapy is fluid restriction.
Frusemide is effective in SIADH.
Vassopressin antagonists (conivaptant,
lixivaptan, tolvaptan) are effective in
correcting euvolemic hyponatremia.

30. THANK YOU