This document discusses sodium regulation and hyponatremia. It outlines that sodium is the main extracellular cation and helps regulate blood pressure and volume. The kidneys aim to balance sodium intake and excretion. Hormones like renin, angiotensin II, aldosterone increase sodium reabsorption while ANP increases excretion. Hyponatremia is defined as a sodium level below 135 mmol/L and can be hypovolemic, euvolemic, or hypervolemic depending on volume status. Evaluation involves assessing volume status, electrolytes, osmolality and urine studies to determine the underlying cause.

1. Presented by: Dr Vineet Chowdhary
Moderator: Dr Chandrashekar Chatterji

2.  Sodium is the most prevalent cation in the extracellular fluid (ECF),
with a normal level of around 135- 145mmol/L & intracellular
concentration of around 10mmol/L
 Total body Sodium is about 5000 mEq in a normal adult person
 Responsible for 90% of total osmolality of ECF
 Daily requirement of sodium is about 100 mEq or 6gm
 Major function of sodium is to maintain ECF volume and therefore
blood pressure
 In normal individuals, the kidney strives to achieve Na+ balance – that
is, to have Na+ excretion equal to Na+ ingestion. The long-term control
of blood pressure is achieved by the excretion or retention of Na+ (and
hence plasma volume) in the kidney

3. Hormones increasing sodium reabsorption:
Renin:
 - Released from the juxtaglomerular apparatus of the kidney
 - Release is stimulated by: raised sympathetic tone, falling plasma volume, and
certain prostaglandins, such as PGE2
 - No direct effects promoting Na+ retention, it controls the renin-angiotensin-
aldosterone axis
Angiotensin II:
 - Levels rise as result of renin release
 - In turn, it stimulates the release of aldosterone
 - Also increases tone in the efferent glomerular arteriole. The net effect is to
enhance Na+ reabsorption from the proximal tubule.
Aldosterone:
 - Steroid hormone released from the adrenal cortex
 - End product of the renin-angiotensin-aldosterone system
 - Acts on the distal tubule and collecting duct to increase Na+ and water
reabsorption (proportionately more Na+ than water)

4. Arginine vasopressin
(AVP), AKA anti-diuretic
hormone (ADH):
 -ADH is produced in neuron cell
bodies in supraoptic and
paraventricular nuclei of the
Hypothalamus, and stored in
posterior pituitary.
 - passive absorption of water from
the collecting
ducts, concentrating the urine
 - Causes a small degree of
Na+ reabsorption, but the
retention of water is
proportionately much greater
·

5. Hormones increasing
sodium excretion:
Atrial Natriuretic
Peptide (ANP):
 - A small peptide
produced from the atrial
wall as a result of atrial
stretching due to
hypervolaemia
 - Acts to increase Na
(and hence water)
excretion by increasing
GFR and blocking Na
reabsorption in the
proximal collecting duct
 Other factors secreted by
the hypothalamus,
termed brain natriuretic
peptides (BNP), may
have similar roles.

6.  Types and distribution
 Include guanylin, uroguanylin, lymphoguanylin
and exogenous peptide toxin produced by
enteric bacteria
 Function
 In gastrointestinal tract, stimulate epithelial
secretion of Cl- and HCO-, causing enhanced
secretion of fluid and electrolyte into the
intestinal lumen.
 in kidney, increase excretion of Na+, Cl-, K+ and
water

7. Serum sodium concentration regulation
 Stimulation of thirst Secretion of ADH Feedback
mechanism of Renin- Angiotensin -Aldosterone Renal handling
of filtered sodium
 Stimulation of thirst :(a) Increase in osmolality is the main driving
force which is sufficient if it increases by 2-3 %. (b) A decrease in
blood pressure or volume by 10-15 %
 Thirst centre is located in the anterolateral centre of the Hypothalamus
 Secretion of ADH is triggered by increase in osmolality by approx 1%
or the vol. or pressure of the vascular sytem. This increases the passive
absorption of water and urea concentrating the urine.
 Renin- Angoitensin- Aldosterone axis acts to cause retention of
sodium in the event of decreased osmolarity

8.  Definition: Hyponatremia is defined as a plasma Na+
concentration <135 mEq/L
 It is due to a relative excess of water in relation to sodium.
 It can result from excessive loss of sodium from excessive
sweating, vomiting, diarrhoea, burns, and diuretics.
 It is a very common disorder, occurring in up to 22% of
hospitalized patients.
 Result of an increase in circulating AVP and/or increased
renal sensitivity to AVP, combined with any intake of free
water; a notable exception is hyponatremia due to low
solute intake.

9.  Patients’ intravascular volume status must be
evaluated to understand further the underlying
problem leading to abnormalities in sodium
physiology.
 Hyponatremia thus is subdivided diagnostically into
three groups, depending on clinical history and
volume status: hypovolemic, euvolemic, and
hypervolemic

10. I- Hypo-osmolar hyponatremia (true hyponatremia)
 Hypovolemic Hyponatremia
 Euvolemic Hyponatremia
 Hypervolemic Hyponatremia
II- Pseudo hyponatremia
 Normal Osmolality
 High Osmolality

11.  Patient dehydrated; reduction in total body sodium exceeds
reduction in total body water
 NON RENAL LOSSES ( Urinary Sodium excretion < 20
mEq/L)- Vomiting, Diarrhea, Third space losses, Pancreatitis,
Burns
 RENAL LOSSES (Urinary Sodium excretion > 20 mEq/L)-
The renal causes of hypovolemic hyponatremia share an
inappropriate loss of Na+-Cl– in the urine, leading to volume
depletion and an increase in circulating AVP. Causes include
reflux nephropathy recovery phase of acute tubular necrosis,
diuretics ,mineralocorticoid deficiency, osmotic diuresis,
ketonuria

12.  “Cerebral salt wasting" : rare cause of hypovolemic
hyponatremia, and inappropriate natriuresis in association
with intracranial disease
 Associated disorders include subarachnoid hemorrhage,
traumatic brain injury, craniotomy, encephalitis, and
meningitis.
 Cerebral salt wasting typically responds to aggressive Na+-
Cl– repletion.

13.  Patient has a normal store of sodium but an excess of total
body water
 The most common form seen in hospitalized patients. The
most common cause is the inappropriate administration of
hypotonic fluid
 The syndrome of inappropriate antidiuresis is the most
common cause of euvolemic hyponatremia
 Other causes include glucocorticoid therapy, stress, drugs ,
hypothyroidism.

14.  Most common cause of euvolemic hyponatremia
 The osmotic threshold and osmotic response curves for
sensation of thirst are shifted downward
 High levels of ADH are secreted intermittently at an abnormally
low threshold or continuously despite low osmolality.
 The presence of hyponatremia plus a urine osmolality higher
than maximal dilution confirms the diagnosis.
 Urinary sodium concentration usually exceeds 30 mEq/L
 The fractional excretion of sodium is greater than 1%.
 Patients with SIADH exhibit a characteristic response to water
restriction; a 2- to 3-kg weight loss is accompanied by correction
of hyponatremia and cessation of salt wasting over 2 to 3 days

16.  Increase in total body water exceeds increase in total body
sodium. Patients are edematous.
 RENAL CAUSES(urinary sodium > 20mEq/L): Acute or Chronic
renal failure
 NON RENAL CAUSES: CHF, Cirrhosis, nephrotic syndrome

18. Normal Osmolarity
 - Due to a measurement error which can result when the solid phase of
plasma (that due to lipid and protein) is increased
 - Typically caused by hypertriglyceridaemia or paraproteinaemia.
High Osmolarity: Translocational hyponatraemia
 - Occurs when an osmotically active solute that cannot cross the cell
membrane is present in the plasma.
 -In the case of the insulinopaenic diabetic patient, glucose cannot enter
cells and hence water is displaced across the cell membrane,
dehydrating the cells and “diluting” the sodium in the serum.
 - This is also the cause of hyponatraemia seen in the TURP syndrome,
in which glycine is inadvertently infused to the same effect.

20.  Severity of symptoms depends upon the severity of
hyponatremia and the rate at which the sodium
concentration is lowered.
 Acute – develops in 48 hours or less. Subjected to
more severe degrees of cerebral edema
 Chronic- develops over 48 hours and brain edema is
less and is well tolerated.
 The signs and symptoms are due to increase in volume
of ICF and increase in volume of brain cells rather
than decrease in serum sodium.

21. SIGNS AND SYMPTOMS OF HYPONATREMIA
Central Nervous System
 Mild – Apathy ,Headache, Lethargy
 Moderate- Disorientation, Psychosis, Agitation, Ataxia
Confusion
 Severe-Stupor, Coma, Pseudobulbar palsy
Tentorial herniation , Cheyne-Stokes respiration, Death
Gastrointestinal System
 Anorexia, Nausea ,Vomiting
Musculoskeletal System
 Cramps Diminished deep tendon reflexes

22.  History and physical examination- to identify hypovolemic
hyponatremia (diarrhoea, vomitting, burns)
 Radiologic imaging - to assess whether patients have a pulmonary or
CNS cause for hyponatremia. CT scanning of the thorax should be
considered in patients at high risk small cell carcinoma
 Laboratory tests- Provide important initial clue in the differential
diagnosis
1. Plasma Osmolality
2. Urine Osmolality
3. Urine Sodium concentration
4. Uric acid level
5. Serum potassium
6. Serum glucose

23. Plasma Osmolality- Normal plasma osmolality is 275-290
mEq/l.
 >290 mEq/L- hyperglycemia or administration of mannitol
 275-290 mEq/L- Hyperlipidemia or hyperproteinemia
 <275 mEq/L- Evaluate volume status
1. Increased Volume- CHF, Cirrhosis, Nephrotic syndrome
2. Euvolemic- SIADH, Hypothyroidism, psychogenic polydipsia
3. Decreased Volume- GI and 3rd space loss, renal losses
 Urine Osmolality-
 Normal value is > 100 mosmol/kg
 Normal to high:
 Hyperlipidemia, hyperproteinemia, hyperglycemia,
SIADH
 < 100 mosmol/kg
 Hypo-osmolar hyponatremia -Excessive sweating,
Burns,Vomiting, Diarrhea , Urinary loss

24.  Urine Sodium
 >20 mEq/L
SIADH, diuretics
 <20 mEq/L
cirrhosis, nephrosis, congestive heart failure, GI loss, skin,
3rd spacing, psychogenic polydipsia
 Uric Acid Level
< 4 mg/dl consider SIADH
 FeNa(Fractional Excretion of Sodium)
 Help to determine pre-renal from renal causes
 Serum glucose -also should be measured; plasma Na+
concentration falls by 1.6 to 2.4 mM for every 100-mg/dL increase
in glucose due to glucose-induced water efflux from cells; this
"true" hyponatremia resolves after correction of hyperglycemia
 Serum Potassium: Hyperkalemia- Renal insufficiency or
Adrenal insufficiency with hypoaldosteronism
Hypokalemia- with metabolic acidosis suggests vomiting or
diuretic therapy

25.  Treatment needs to be individualized considering etiology, rate of
development, severity and clinical signs and symptoms
 Hyponatremia which developed quickly needs to be treated fast
whereas slow developing hyponatremia should be corrected slowly
GOALS of THERAPY:
1. To raise the plasma sodium concentration at a slow rate
2. To replace sodium or potassium deficit or both
3. To correct underlying etiology
BASIC PRINCIPLES OF CORRECTION:
 Rapid correction is indicated in acute (<48hours) symptomatic or
severe hyponatremia.(serum Na <120 mEq/L)
 In chronic cases patients are at little risk, however rapid correction can
lead to demylination. Use slower acting therapies like water restriction

26. Treatment of acute symptomatic hyponatremia
 Hypertonic 3% saline (513 mM) to acutely increase plasma Na+
concentration by 1–2 mM/h to a total of 4–6 mM; alleviate severe
acute symptoms, after which corrective guidelines for "chronic"
hyponatremia are appropriate
 The increase in plasma Na+ concentration can be highly
unpredictable during treatment ,plasma Na+ concentration
should be monitored every 2–4 h during treatment
 Vasopressin antagonists do not have an approved role in the
management of acute hyponatremia.
Treatment of chronic hyponatremia
 Rate of correction should be comparatively slow
 <8–10 mM in the first 24 h and <18 mM in the first 48 h to avoid
ODS

27.  Hypovolemic hyponatremia will respond to intravenous
hydration with isotonic normal saline, with a rapid
reduction in circulating AVP and a brisk water diuresis.
Diuretics induced hyponatremia is treated with saline and
potassium supplementation
 Hypervolemic hyponatremia responds to no salt, water
restriction(intake< urine output), and loop diuretics
 Euvolemic hyponatremia will respond to successful
treatment of the underlying cause, with an increase in
plasma Na+ concentration
 Regardless of the initial rate of correction, chosen acute
treatment is stopped once
1. patient’s symptoms are abolished
2. A safe plasma sodium (120-125 mEq/L) is achieved

28. SPECIFIC THERAPY:
 1. Removal of responsible drugs- diuretics, chlorproamide etc
 2. Management of physical stress or post operative pain
 3. Specific treatment of underlying cause
 4. Vasopressin antagonists (vaptans) are highly effective in
treating SIAD and hypervolemic hyponatremia, reliably
increasing plasma Na+ concentration as a result of their aquaretic
effects (augmentation of free-water clearance). Most of these
agents specifically antagonize theV2 vasopressin receptor
TO CALCULATE NEED OF REPLACEMENT SODIUM
CONTAINING FLUID:
 0.9% saline (154mEq/L) and 3% NaCl- hypertonic saline (513
mEq/L) are the only two routinely used I.V. fluids . However
0.9% NS is not used to correct hyponatremia in SIADH

29.  estimate SNa change on the basis of the amount of Na in
the infusate
 ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
 ΔSNa is a change in SNa
 [Na + K]inf is infusate Na and K concentration in 1 liter of
solution
 Total Body Water= 0.6* B.W(kg) in children and nonelderly man
=0.5*B.W.(kg) in nonelderly woman and
elderly man
=0.45*B.W.(kg) in elderly women

30.  Asymptomatic or Chronic
 SIADH
 response to isotonic saline is different in the SIADH
 In hypovolemia both the sodium and water are retained
 Sodium handling is intact in SIADH
 Administered sodium will be excreted in the urine, while
some of the water may be retained possibly worsening the
hyponatremia
 Water restriction
0.5-1 liter/day
 Salt tablets
 Demeclocycline
 Inhibits the effects of ADH
 Onset of action may require up to one week

31.  Hypernatremia is defined as an increase in the plasma Na+
concentration to >145 mM. Considerably less common than
hyponatremia, hypernatremia nonetheless is associated
with mortality rates as high as 40–60%.Hypernatremia is
caused by a relative deficit of water in relation to sodium
which can result from
 Net water loss: accounts for majority of cases
 pure water loss
 hypotonic fluid loss
 Hypertonic gain results from iatrogenic sodium loading

32. Net water loss
Pure water loss
•Unreplaced insensible losses (dermal and respiratory)
•Hypodipsia
•Neurogenic diabetes insipidus
 Post-traumatic
 tumors, cysts, histiocytosis, tuberculosis, sarcoidosis
 Idiopathic
 aneurysms, meningitis, encephalitis, Guillain-Barre
syndrome
 Congenital nephrogenic diabetes insipidus
 Acquired nephrogenic diabetes insipidus
 Renal disease (e.g. medullary cystic disease)
 Hypercalcemia or hypokalemia
 Drugs (lithium, methoxyflurane, amphotericin B, vasopressin
V2-receptor antagonists)

33.  Hypotonic fluid loss
• Renal causes
Loop diuretics
Osmotic diuresis (glucose, urea, mannitol)
Post obstructive diuresis
Polyuric phase of acute tubular necrosis
• Gastrointestinal causes
Vomiting
Nasogastric drainage
Entero cutaneous fistula
Diarrhea
Use of osmotic cathartic agents (e.g., lactulose)
• Cutaneous causes
Burns
Excessive sweating

34. Hypertonic sodium gain
Hypertonic sodium bicarbonate infusion
Ingestion of sodium chloride
Ingestion of sea water
Hypertonic sodium chloride infusion
Primary hyper-aldosteronism
Cushing’s syndrome

35.  The symptoms of hypernatremia are predominantly
neurologic.
 Altered mental status is the most common manifestation,
ranging from mild confusion and lethargy to deep coma.
 The sudden shrinkage of brain cells in acute hypernatremia
may lead to parenchymal or subarachnoid haemorrhages
and/or subdural hematomas; however, these vascular
complications are encountered primarily in paediatric and
neonatal patients
 Osmotic damage to muscle membranes also can lead to
hypernatremic rhabdomyolysis

36. HISTORY AND PHYSICAL EXAMINATION:
 The history should focus on the presence or absence of thirst, polyuria,
and/or an extrarenal source for water loss, such as diarrhoea
 The physical examination should include a detailed neurologic exam
and an assessment of the ECFV; patients may be hypovolemic, with
reduced JVP and orthostasis
 Accurate documentation of daily fluid intake and daily urine output
LAB INVESTIGATIONS:
 Measurement of serum and urine osmolality in addition to urine
electrolytes
- The appropriate response to hypernatremia and a serum osmolality
>295 mosmol/kg is an increase in circulating AVP and the excretion of
low volumes (<500 mL/d) of maximally concentrated urine, i.e., urine
with osmolality >800 mosmol/kg

37.  Diabetes insipidus may result from a deficiency of ADH
(vasopressin) or inability of the kidney to produce a
hypertonic medullary interstitium
 Diabetes insipidus is characterized by production of a large
volume of dilute urine.
 Deficiency of vasopressin is known as central diabetes
insipidus .Vasopressin deficiency is seen after pituitary
surgery, basal skull fracture, and severe head injury.
 Nephrogenic diabetes insipidus is defined as renal tubule
cell insensitivity to the effects of vasopressin.
 In patients with DI a significant amount of body water is
lost in a short period, which can cause profound
hypovolemia

38.  Patients with continued urine output of more than 100
mL/hr who develop hypernatremia should be evaluated for
diabetes insipidus by determining the osmolalities of
urine and serum.
 If the urine osmolality is less than 300 mOsm/L, and
serum sodium exceeds 150 mEq/L, the diagnosis of diabetes
insipidus is likely.
 Patients with central DI should respond to the
administration of intravenous, intranasal, or oral
Desmopressin.
 Patients with NDI due to lithium may reduce their polyuria
with amiloride (2.5–10 mg/d)
 Thiazides may reduce polyuria due to NDI
 Occasionally (NSAIDs) have been used to treat polyuria
associated with NDI

39. A two-pronged approach:
 Addressing the underlying cause
 Correcting the prevailing hypertonicity
RATE OF CORRECTION:
Hypernatremia that developed over a period of hours (accidental
loading)
 Rapid correction improves prognosis without cerebral edema
 Reducing Na+ by 1 mmol/L/hr appropriate
Hypernatremia of prolonged or unknown duration
 a slow pace of correction prudent
 maximum rate 0.5 mmol/L/hr to prevent cerebral edema
 A targeted fall in Na+ of 10 mmol/L/24 hr

40.  Reduce serum sodium concentration to 145 mmol/L
 Make allowance for ongoing obligatory or incidental losses of
hypotonic fluids that will aggravate the hypernatremia
 In patients with seizures prompt anticonvulsant therapy and
adequate ventilation
Administration of Fluids
 Water ideally should be administered by mouth or by
nasogastric tube as the most direct way to provide free water, i.e.,
water without electrolytes.
 Alternatively, patients can receive free water in dextrose-
containing IV solutions such as 5% dextrose

41.  Hypernatremia with ECF vol contraction-
Isotonic saline is given initially till ECF vol is restored.
Subsequently water deficit can be replaced with water by
mouth or I.V. 5% dextrose or 0.45% NaCl
 Hypernatremia with increased ECF volume: since
hypernatremia is secondary to solute administration it can
be rapidly corrected . Patients are volume overloaded- loop
diuretic is given along with water to remove sodium excess

42.  If at all possible, hyponatremia, especially if
symptomatic, should be corrected prior to surgery.
Level above 130mEq/L is considered safe
 If lower than 130 mEq/L it can be the cause of :-
 1. Cerebral edema
 2. Decreased MAC
 3. Post op agitation and confusion
 4. Problems of hypervolemia
 If the surgery is urgent, then appropriate corrective
treatment should continue throughout the surgery
and into the postoperative period.

43.  Frequent measurement of serum sodium is necessary to
avoid overly rapid correction of hyponatremia with
resultant osmotic demyelination or overcorrection
resulting in hypernatremia.
 Treatment of the underlying cause of the hyponatremia
should also continue throughout the perioperative period.
 Induction and maintenance of anesthesia in patients with
hypovolemic hyponatremia are fraught with the risk of
hypotension. In addition to fluid therapy, vasopressors
and/or inotropes may be required to treat the hypotension
 Hypovolemic patients are sensitive to the vasodilating and
negative inotropic effects of the volatile
anesthetics, barbiturates, and agents associated with
histamine release
(morphine, meperidine, curare, atracurium).

44.  Dosage requirements for other drugs must also be reduced
to compensate for decreases in their volume of
distribution. Hypovolemic patients are particularly
sensitive to sympathetic blockade from spinal or epidural
anesthesia.
 If an anesthetic must be administered prior to complete
correction of the hypovolemia, ketamine may be the
induction agent of choice for general anesthesia; etomidate
may be a suitable alternative.

45.  It involves the resection of the prostate via a
cystoscope with continuous irrigation of the
bladder.
 The irrigating fluid is a nonelectrolyte fluid
containing glycine, sorbitol, or mannitol, and this
fluid may be absorbed rapidly causing volume
overload, hyponatremia, and hypo-osmolality.
 An awake patient permits detection of the signs of
hyponatremia, including nausea, vomiting, visual
disturbances, depressed level of consciousness,
agitation, confusion, coma, seizures, muscle
cramps, and death.

46.  Cerebral edema occurs at or below a serum level of 123
mEq/L, and cardiac symptoms occur at 100 mEq/L. It
can result in pulmonary edema, hypertension, and
heart failure.[19]
 Monitoring - direct neurologic assessment in the
patient under regional anesthesia
- Measurement of serum sodium concentration and
osmolality in the patient under general anesthesia.
 Treatment -Terminating the surgical procedure
-Diuretics if needed for relief of cardiovascular
symptoms
- Hypertonic saline administration if severe neurologic
symptoms are present or the serum sodium
concentration is less than 120 mEq/L.

47.  Overly rapid correction of hyponatremia (>8–10 mM in 24 h or 18
mM in 48 h) also is associated with a disruption in integrity of
the blood-brain barrier.
 The lesions of ODS classically affect the pons
 Clinically, patients with central pontine myelinolysis can present
one or more days after overcorrection of hyponatremia with
para- or quadraparesis, dysphagia, dysarthria, diplopia, a
"locked-in syndrome," and/or loss of consciousness.
 Other regions of the brain also can be involved in ODS.
 In order of frequency, the lesions of extrapontine myelinolysis
can occur in the cerebellum, lateral geniculate body, thalamus,
putamen, and cerebral cortex or subcortex.

48.  Development of ataxia, mutism, parkinsonism, dystonia,
and catatonia is seen in these
 Relowering of plasma Na+ concentration after overly rapid
correction can prevent or attenuate ODS
 However, even appropriately slow correction can be
associated with ODS, particularly in patients with
additional risk factors; these factors include alcoholism,
malnutrition, hypokalemia, and liver transplantation.

49. Severe
hyponatremia
followed by
extrapontine
myelinolysis

50.  Osmolar gap is considered significant when the difference
between the measured and calculated osmolarity is > 10
 Some critically ill patients have an unexplained osmolar gap
which is thought to result from escape of osmotically active
intracellular solutes into extracellular fluid
 Increased membrane permeability to Na and decreased active
removal of sodium from the cells by energy dependent cation
exchange pump leads to redistribution hyponatremia with
increased osmolar gap- a concept called sick cell syndrome.
 This state has been described during a great variety of human
diseases such as traumatic shock, diabetic ketoacidosis, lactic
acidosis and multiple organ failure
 Both the osmolar gap and hyponatremia correct simultaneously
in this condition as the primary illness is treated

51.  If at all possible, surgery should be delayed until
the hypernatremia has been corrected or at least
until symptoms have abated.
 Frequent serum sodium measurements will be
required perioperatively, and invasive
hemodynamic monitoring may be useful.
 Hypovolemia will be exacerbated by induction
and maintenance of anesthesia and prompt
correction of hypotension with fluids,
vasopressors, and/or inotropes may be required.
 Increased MAC seen in animal studies