This document discusses sodium metabolism and disorders of sodium concentration. It provides details on: - Water distribution in the body and fluid compartments - Causes and types of hyponatremia, including hypovolemic, hypervolemic, and euvolemic hyponatremia - Evaluation and management of hyponatremia, including treatment based on severity and rate of sodium correction - Causes and clinical features of hypernatremia The document is a comprehensive review of sodium disorders and approaches to diagnosis and treatment of hypo- and hypernatremia.

1. SODIUM METABOLISM
Dr Kaleem Ahmad
JR III
Pulmonary Medicine

2.  Water is the most abundant constituent in the body comprising
approximately 50% of body weight in women and 60% in men.
 55-75% is intracellular (intracellular fluid [ICF] ) and 25-45% is
extracellular (extracellular fluid [ECF] ) .
 The ECF is further subdivided into intravascular (plasma water) and
extravascular (interstitial) spaces in a ratio of 1 :3.
 The solute or particle concentration of a fluid is known as its osmolality
expressed as milliosmoles per kilogram of water (mOsm/kg) .
 The major ECF particles are Na+ and its accompanying anions Cl- and
HCO3- whereas K+ and organic phosphate esters (ATP， creatinine
phosphate and phospholipids) are the predominant ICF osmoles.
..

3.  Vasopressin secretion water ingestion and renal water transport
collaborate to maintain human body fluid osmolality between
280 and 295 mOsm/kg

4. SODIUM DISORDER
 Disorders of serum Na+ concentration are caused by
abnormalities in water homeostasis leading to changes
in the relative ratio of Na+ to body water.
 Water intake and circulating AVP constitute the two
key.
 85-90% of body Na+ is extracellular and the ECF
volume (ECFV) is a function of total-body Na+
content
 99.6% filtered Na+ is reabsorbed in kidney

5. HYPONATREMIA
 Hyponatremia is defined as a plasma Na+
concentration < 135 m.mol
 Very common disorder.
 Occurring in up to 22% of hospitalized patients.
 Depending on clinical history and volume status
divided into
a) Hypovolemic Hyponatremia
b) Euvolumic Hyponatremia
c) Hypervolemic Hyponatremia

6. HYPOVOLUMIC HYPONATREMIA
 Characterized by true deficiency of both Na+ and water
 Increase in circulating AVP level.
 Increased free water intake.
 GI loss (e.g. vomiting diarrhea tube drainage)
 Insensible loss (sweating, burns)
 Primary adrenal insufficiency
 Salt-losing nephropathies
 Phase of acute tubular necrosis.
 Thiazide diuretics

7.  Glycosuria,
 Ketonuria,
 Bicarbonaturia
 Cerebral salt wasting

8. Hypovolumia
Total body water decrease
Total body sodium much decrease
U Na GREATER THAN 20
 Renal losses
 Diuretic excess
 Mineralocorticoides deficiency
 Salt losing deficiency
 Bicarbonaturia with renal
tubular acidosis and metabolic
alkalosis
 Ketonuria, osmotic diuresis
 Cerebral salt wasting syndrome
 U Na less than 20
 Extra renal losses
 Vomiting
 Diarrhea
 Third spacing of fluid
 Burns
 Pancreatitis
 Trauma

9. HYPERVOLUMIC HYPONATREMIA
 Patients with hypervolemic hyponatremia develop an increase in total-
body Na+Cl- that is accompanied by a proportionately greater
increase in total body water leading to a reduced plasma Na+
concentration:-
 Congestive heart failure [CHF]
 Cirrhosis
 Nephrotic syndrome
 Acute or chronic renal failure，
 Characterized by development of pitting edema (about 5 litres of
excess water need to be retained to produce definite pitting edema in
an avereged sized adult)

10. Hypervolumia
Total body water much increase
Total body sodium increase
 U Na greater than 20
 Acute or chronic renal failure
 U Na less than 20
 Nephrotic syndrome
 Cirrhosis
 Cardiac failure

11. EUVOLEMIC HYPONATREMIA
 Secondary adrenal insufficiency due to pituitary
disease;
 Moderate to severe hypothyroidism, with correction
after achieving euthyroid state.
 Syndrome of inappropriate antidiuresis (SIAD)

12. URINARY SODIUM GREATER THAN 20
•Glucocorticoides deficiency
•Hypothyroidism
•Stress
•Drugs
•Syndrome of inappropriate antidiuretic harmone
secretion (SIAD)

13. LOW SOLUTE INTAKE AND HYPONATREMIA
 Alcoholics (beer potomania)
 Extreme vegetarian diets
 Tea toast diet
PSEUDOHYPONATREMIA
 Expansion of extracellular fluid with isotonic fluids that do not contain Na
 There is no transcellular shift of water but the [Na+] decreases
e.g. Hypertriglyceridemia
Hyperproteinemia( as in Multiple Myeloma)
Rise in plasma lipids of 4.6 g/L or plasma protein
concentrations greater than 10 g/dL will decrease the sodium
concentration by approximately 1 mEq/L.

14. Clinical diagnosis
 Symptoms due to hyponatremia depends on its severity and the rate at
which it evolves.
 The symptoms primarily neurologic, due to development of cerebral
edema within a rigid skull.
 Symptoms are :
Headache, lethargy,
Confusion, gait disorder,
Nausea, vomiting
In severe hyponatremia seizures, coma, brain-stem herniation,
permanent brain damage or death.
 Hypo-natremia < 135 mmol/lit mild
< 130 mmol/lit moderate
< 120 mmol/lit severe

15. Severe and Acute Hyponatremia
 Severe hyponatremia (Na+<120meq/l) and rapid
development of hyponatremia (<48 hours)
 A key complication is normocapnic or hypercapnic
respiratory failure.
 Normocapnic respiratory failure is noncardiogenic,
neurogenic pulmonary edema, with a normal pulmonary
capillary wedge pressure.

16.  Causes of acute hyponatremia
 Iatrogenic
 Postoperative premenopausal women
 Hypotonic fluids with cause of ↑ vasopressin
 Glycine irrigation: TURP, uterine surgery
 Colonoscopy preparation
 Recent institution of thiazides
 Polydipsia
 Exercise induced
 Multifactorial, e.g., thiazide and polydipsia

17. Persistent chronic hyponatremia
 Pathogenesis:
Efflux of organic osmolytes (creatine, betaine, glutamate, myo-inositol,
and taurine) from brain cells,decrease intracellular osmolality decrease
water entry.(compensation)
Complete within 48 h, time period defines chronic hyponatremia.
 Symptom:
Vomiting, nausea
Confusion and seizures
Subtle gait and cognitive defects
Increases risk of falls
Risk of bony fractures (hyponatremia associated reduction in bone
density)

19. Diagnostic Evaluation of Hyponatremia
 Clinical assessment
 Underlying cause
 Detailed drug history
Drugs that stimulate release of AVP or enhance its action on
vasopressin V2 receptor
Chlorpropamide Cyclophosphamide
SSRls NSAIDS
Tricyclic antidepressants AVP analogues
Clofibrate Desmopressin
Carbamazepine Vasopressin
Nicotine Ifosfamide
Antipsychotic drugs
MDMA“ecstasy”(3,4-methylenedioxymethamphetamine)

20.  Multifactorial,
 Consider all the possible causes
 In case of true salt and water depletion
Dehydration
Shock
Thrist
Severa cramps in the legs thigh and abdomen
 Metabolic alkalosis in case of vomiting and metabolic
acidosis in diarrhoea.

21.  Features of low volume status
Diminished skinTurgor
Dry oral mucous membranes
 More reliable signs of hypovolemia
Decreased jugular venous pressure (JVP)
Orthostatic tachycardia (an increase of > 15-20 beats/min
upon standing)
Orthostatic hypotension (a >10-20 mmHg drop in blood
pressure on standing) .
 More severe fluid loss leads to hypovolemic shock
Patients may exhibit peripheral cyanosis cold
Extremities oliguria and altered mental status

22. LABORATORY TEST
 Serum osmolality
To exclude pseudohyponatremia which is defined as the
coexistence of hyponatremia with a normal or increased
plasma tonicity.
In hyponatremia plasma osmolality is generally less than
275 mOsm/kg
 Serum Na K
Hyperkalemia may suggest adrenal insufficiency or
hypoaldosteronism
 Urine Na K
To differentiate various causes of water loss

23.  Serum glucose
Plasma Na+ concentration falls by 1.6-2.4 mM for every 100
mg/dL increase in glucose due to glucose-induced water efflux
from cells.
 Serum uric acid
Patients with SIAD-type physiology will typically be
hypouricemic (serum uric acid <4 mg/dL)，
Volume-depleted patients will often be hyperuricemic.

24.  Urine Osmolality
A urine osmolality <100 mOsm/kg is suggestive of polydipsia
Urine osmolality >400 mOsm/kg indicates that AVP excess is
playing a more dominant role
Whereas intermediate values are more consistent with
multifactorial pathophysiology
 Serum protein & lipid profile
To exclude causes of pseudo-hyponatremia

25.  THYROID， ADRENAL， AND PITUITARY FUNCTION
Hypothyroidism and secondary adrenal failure due to pituitary
insufficiency are important causes of euvolemic hyponatremia.
Whereas primary adrenal failure causes hypovolemic hyponatremia.
 RADIOLOGY
Chest XRay- PA view
CT of Thorax & Brain

26. MANAGEMENT
Three major considerations to guide therapy for
hyponatremia.
1. Severity of symptoms
2. Risk for ODS (osmotic demylenation syndrome)
It occurs, if plasma Na+ concentration is corrected, by > 8-10 mM
within the first 24h and/or by >18 mM within the first 48h.
3. Highly unpredictable response
Once the urgency in correcting the plasma Na+ concentration
has been established and appropriate therapy instituted, the
focus should be on treatment or withdrawal of the underlying
cause.

27.  Hypovolemic hyponatremia will respond to intravenous
hydration with isotonic normal saline with a rapid reduction in
circulating AVP and a brisk water diuresis
 Hypervolemic hyponatremia due to CHF will often respond
to improved therapy of the underlying cardiomyopathy e.g.
following the institution or intensification of angiotensin-converting
enzyme (ACE) inhibiter.
 Finally patients with hyponatremia due to beer potomania and low
solute intake will respond very rapidly to intravenous saline and the
resumption of a normal diet.
 Notably patients with beer potomania have a very high risk of
developing ODS due to the associated hypokalemia alcoholism
malnutrition and high risk of overcorrecting the plasma Na+
concentration

28.  Water deprivation has long been cornerstone of the therapy of
chronic hyponatremia
 The urine-to-plasma electrolyte ratio, (urinary [Na+]+[K+]/plasma
[Na+]) can be exploited as a quick indicator of electrolyte-free water
excretion
 Patients with a ratio of >1 should be more aggressively restricted (<500
mL/d)， those with a ratio of ~1 should be restricted to 500-700 mL/d
and those with a ratio <1 should be restricted to <1L/d
 Hypokalemia should be corrected.

29.  PHARMACOTHERAPY
Many patients with SIAD respond to combined therapy with oral
furosemide 20 mg twice a day and oral salt tablets.
Demeclocycline
 AVP antagonists (vaptans) are highly effective in SIAD and in
hypervolemic hyponatremia due to heart failure or cirrhosis
increasing plasma Na+ concentration due to their aquarectic effects
(augmentation of free water clearance) .
Antagonize V2 AVP recepter

30.  Treatment of acute symptomatic hyponatremia should include
hypertonic 3% saline (513 mM ) to acutely increase plasma Na+
concentration by 1-2 mM/h to a total of 4-6 mM.
 The traditional approach to calculate Na+ deficit
= 0.6 x body weight x (target plasmaNa+
concentration - starting plasma Na+ concentration)
 ，
 Followed by a calculation of the required rate.
A widely used formula is the Adrogue-Madias formula.
Change in serum Na+ with infusing solution (mM/l/h) =
[infusate (Na + K)]-serum Na/ (total body water +1)

31.  Plasma Na+ concentration should be monitored every 2-4 h
during treatment.
 In patients with severe symptomatic hyponatremia, the rate of
sodium correction should be 6 to 12 mEq per L in the first 24
hours and 18 mEq per L or less in 48 hours.
 A bolus of 100 to 150 mL of hypertonic 3% saline can be given to
correct severe hyponatremia.
 Chronic hypernatremia should be corrected at a rate of 0.5
mEq per L per hour, with a maximum change of 8 to 10 mEq per
L in a 24-hour period.

32.  WE MUST KNOW FLUID COMPOSITION COMMONLY
USED:
154meq/l in 0.9%NS
513meq/l in 3%NS
77meq/l in 0.45%NS
zero meq/l in D5W, D10W, D25W

33. THANK YOU

34. HYPERNATREMIA
 Hypernatremia is defined as an increase in the plasma Na+concentration
to>145mM.
 less common than hyponattremiai
 Mortality rate as high as 40% is reported with hypernatremia, though it is
uncommonly identified as the primary cause of death.
 ETIOLOGY
 Usually the result of a combined water and electrolyte deficit with losses of water in
excess of Na+.
 Elderly individuals and neonates are more susceptible.
 hypernatremia may rarely have a central defect in hypothalamic osmoreceptor
function， with a mixture of both decreased thirst and reduced A VP secretion.

35. causea
Insensible losses
fever
exercise
heat exposure
severe burns
mechanicalventilation.
 iatrogenic administration of excess Na+ can be causative， for example after IV administration of
excessive hypertonic Na+ -Cl- or Na+ -HC03-
 Diarrhea is in turn the most common gastrointestinal
cause of hypernatremia.
 Notably osmotic diarrhea and viral gastroenteritides
typically generate stools with Na+ and K+ < 1 00 mM， thus leading to water loss and hypernatremia.
 In contrast secretory diarrhea typically results in isotonic stool
and thus hypovolemia with or without hypovolemic hyponatremia.

36.  osmotic diuresis secondary to hyperglycemia， excess urea，
postobstructive diuresis， or mannitol;
 diabetes insipidus (DI)
Central
Nephrogenic (renal resistance to AVP)
 Hypercalcemia hypokalemia
 lithium ifosfamide and several antiviral agents
 gestational DI ( due to circulating placental protease with
vasopressinase activity)

37.  linical Features
Hypernatremia increases osmolality of the ECF generating an osmotic gradient
between the ECF and ICF, an eff1ux of intracellular water, and cellular
shrinkage.
 predominantly neurologic.
 Altered mental status is the most frequent 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 hemorrhages and/or subdural hematomas.
 hypernatremic rhabdomyolysis (Osmotic damage to muscle membranes)

38. Diagnostic Approach
 history should focus on
 presence or absence of thirst
 polyuria
 extrarenal source for water loss
 The physical examination should include a detailed
neurologic exam and an assessment of the ECF volume
status.

39.  Laboratory investigation
 measurement of serum ( >295 mOsm/kg ) and urine osmolality (>800
mOsm/kg)
 urine electrolytes
 circulating AVP level
 Urinary and serum glucose
 a excretion of low volumes (<500 mL!d) of maximally concentrated
urine， i.e.， urine with osmolality >800 mOsm/kg;
 water loss is primarily responsible for the generation of hypernatremia

40. NEPHROGENIC VERSUS CENTRAL DIABETES
INSIPIDUS
 Patients with NDI will fail to respond to DDAVP with a
urine osmolality that increases by<50% or < 150
mOsm/kg from baseline in combination with a normal
or high circulating AVP level .
 patients with central DI will respond
to DDAVP， with a reduced circulating AVP level.

41. The underlying cause of hypernatremia should be identified and
corrected，be it drugs，hyperglycemia，hypercalcemia，
hypokalemia，or diarrhea.
 It is imperative to correct hypernatremia slowly
 to avoid cerebral edema， typically replacing the calculated free water
deficit over 48 h .
 Notably， the plasma Na+ concentration should be corrected by no
more than 10 mM/d， which may take longer than 48 h in patients
with severe hypernatremia (> 160 mM).
 A rare exception is patients with acute hypernatremia (<48 h) due to
sodium loading who can safely be corrected rapidly at a rate of 1 mM/h.
 Water should ideally be administered by mouth or by nasogastric tube

42.  patients can receive free water in dextrose-containin g IV
solutions， such as 5% dextrose (DsW);
 blood glucose should be monitored

 it may be appropriate to initially treat with hypotonic saline
solutions (1/4or1/2 normal saline); normal saline is usualy
inappropriate
 in the absence of very severe hypernatremia where normal
saline is proportionally more hypotonic relative to plasma
or frank

43. Intravenous intranasal or oral DDAVP.
Amiloride(2.5-10 mg/d)
Thiazides
NSAIDs

44.  MANAGEMENT OF HVPERNATREMIA
 Water Deficit
 1 . Estimate tota l-body water (TßW): 50% of body weight in women and 60% in men
 2. Ca lculate free-water deficit [(N扩1 40)/1 40}x TßW
 3. Administer deficit over 48-72 h without decrease in plasma Na+ concentration by > 1 0
mM/24 h
 Ongoing Water Losses
 4. Ca lculate free-water clearance， C，H，o
 r u. + U I
 C H_Q = V x 门一半一-一--'- 1
 1 P J .'ò
 where V is urinary 、口lume， UNe is urinary [Na可， UK is urinary [K可， and PNe is
 plasma [Na吁
 Insensible Losses
 5. - 1 0 mL/kg per day: less if、巳ntilated， more if febril巳
 Total
 6. Add com ponents to determine water de有ζit and ongoing water loss;
 ζorrect the water de白cit over 48-72 h and replace daily water loss. Avoid