This document discusses serum sodium disorders caused by abnormalities in water homeostasis. It focuses on SIADH (syndrome of inappropriate antidiuretic hormone secretion), a disorder of impaired water excretion caused by excessive antidiuretic hormone (ADH) secretion or action. SIADH is the most common cause of hyponatremia. Treatment involves fluid restriction and sometimes intravenous saline or vasopressin receptor antagonists to raise sodium levels.

1. Dr .Raviraj

2. Introduction
 Disorders of serum Na+ concentration are caused by
abnormalities in water homeostasis that lead to
changes in the relative ratio of Na+ to body water.
 Water intake and circulating AVP constitute the two
key effectors in the defense of serum osmolality;
 defects in one or both of these defense mechanisms
cause most cases of hyponatremia and
hypernatremia.
 Hypontremia- defined as a serum sodium
concentration below 135 meq/L

3. Hyponatremia
Serum OSM
Low
Normal High
Hypotonic
Hyponatremia
ECFv *
Low
Normal
High
Hyperglycemia
Mannitol
Marked hyperlipidemia
(lipemia, TG >35mM)
Hyperproteinemia
(Multiple myeloma)
•CHF
•Cirrhosis
•Nephrotic
syndrome
•Hypothyroidism
•AI
•SIADH
•Reset Osmostat
•Water Intoxication
1° Polydipsia
TURP post-op
Renal loss (UNa > 20)
•Diuretics
•Thiazide
•K-sparing
•ACE-I, ARB
•IV RTA, Hypoaldo
• Cerebral salt wasting
Extra-renal loss (UNa <10)
•Bleeding
•Burns
•GI (N/V, diarrhea)
•Pancreatitis
*Note: all have ↑ADH
•SIADH: inappropriate
•Rest: appropriate

4.  ADH- AVP- Anti Diuretic Hormone
 Synthesized in hypothalamus  Transported down to
posterior pituitary  Released in response to
hyperosmolality (major stimuli, mediated through
osmoreceptors in hypothalamus) or hypovolemia (via
baroreceptors in left atrium, aortic arch, etc)
 Binds to V2 receptors in collecting tubules
 stimulates cyclic adenosine monophosphate
 leads to insertion of aquaporin-2 channels into apical
membranes of collecting ducts
 The goal is to facilitate the transport of solute-free water

5.  Stimulation of ADH release
 Hypertonicity, Volume contraction, Hypotension
 Nausea/emesis
 Hypoglycaemia
 Severe heart failure, Severe liver failure
 Hypothyroidism, Adrenal insufficiency
 Ethanol
 Hormones/drugs
 Angiotensin II, Sympathetic amines (α1 agonists) Histamine,
Bradykinin, Opioids (μ agonists),
 Nicotine, Antipsychotics/antidepressants, Ifosfamide
Chlorpropamide, Carbamazepine, Narcotics, Vincristine,
Clofibrate.

6.  Inhibition of ADH release
 Hypotonicity, Volume expansion, Hypertension
 Hormones/drugs - Opioids (κ and agonists) Sympathetic
amines (β agonists) Acetaminophen
 Drugs that potentiate renal action of ADH
 Chlorpromazine
 Cyclophosphamide
 Non-steroidal anti-inflammatory drugs
 Drugs that cause water retention by unknown
mechanism
 Haloperidol, Fluphenazine
 Amitriptyline, Thioridazine
 Fluoxetine, Sertraline
 Ecstasy

7.  SIADH-
 is a disorder of impaired water excretion caused by
the inability to suppress secretion or due to excessive
secretion and action of Antidiuretic hormone .
 If water intake exceeds the reduced urine output
(concentrated Urine), the ensuing water retention
leads to the development of hyponatremia.
 Most common cause of HYPOOSMOLAR
EUVOLEMIC Hyponatremia

8.  Pathophysiology
 Inappropriate ADH secretion
 ADH-induced water retention Hyponatremia
 Volume expansion activates secondary natriuretic
mechanisms, resulting in sodium and water loss and
the restoration of near-euvolemia.
 The net effect is that, with chronic SIADH, sodium
loss is more prominent than water retention .
 However, since there is no impairment in volume
regulatory hormones (aldosterone and natriuretic
peptides), patients with SIADH are euvolemic
unless there is a second problem leading to salt loss

9. Increased AVP
Water retention
Plasma dilution
Natriuresis
Hyponatremia
Suppression of
RAAS
Increased ANP
Why Hyponatremia & Natriuresis
in SIADH?
Natriuresis

10.  Etiology
Neoplasms
Carcinomas
Lung
Duodenum
Pancreas
Ovary
Bladder, ureter
Other neoplasms
Thymoma
Mesothelioma
Bronchial adenoma
Carcinoid
Gangliocytoma
Ewing's sarcoma
Head trauma (closed and
penetrating)
Infections
Pneumonia, bacterial or viral
Abscess, lung or brain
Cavitation (aspergillosis)
Tuberculosis, lung or brain
Meningitis, bacterial or viral
Encephalitis
AIDS
Vascular
Cerebrovascular occlusions,
hemorrhage
Cavernous sinus thrombosis
Genetic
X-linked recessive
(V2 receptor gene)

11. Neurologic
Guillain-Barré syndrome
Multiple sclerosis
Delirium tremens
Amyotrophic lateral sclerosis
Hydrocephalus
Psychosis
Peripheral neuropathy
Congenital malformations
Agenesis corpus callosum
Cleft lip/palate
Other midline defects
Metabolic
Acute intermittent porphyria
Pulmonary
Asthma
Pneumothorax
Positive-pressure respiration
Drugs
Vasopressin or desmopressin
Chlorpropamide
Oxytocin, high dose
Vincristine
Carbamazepine
Nicotine
Phenothiazines
Cyclophosphamide
Tricyclic antidepressants
Monoamine oxidase inhibitors
Serotonin reuptake inhibitors

13.  Investigations sent for diagnosis of SIADH:
 Serum Na+, potassium, chloride, and bicarbonate
 Plasma osmolality
 Urine Sodium
 Urine osmolality
 Serum creatinine
 Blood urea nitrogen
 Blood glucose
 Serum uric acid
 Serum cortisol
 Thyroid-stimulating hormone

14. SIADH- Diagnosis
 Normal ECFv (or slightly increased)- Euvolemic
 ↓ serum Na/OSM (< 275 mM)- Hypoosmolar
 UOSM > 100 mosm/kg,
 UNa > 40 mEq/L
 Low plasma uric acid (< 238 umol/L)
 Low- BU/Creatinine
 Hypothyroidism & AI ruled out, No Diuretics
 SIADH should be diagnosed when these findings occur in the setting of
otherwise normal cardiac, renal, adrenal, hepatic, and thyroid function; in
the absence of diuretic therapy; and in absence of other factors known to
stimulate ADH secretion, such as hypotension, severe pain, nausea, and
stress.
 Failure to correct Hyponatremia with 0.9% saline and
correction with fluid restriction

15. Clinical Manifestations of Hyponatremia
 Hypoosmolality is associated primarily with a broad
spectrum of neurologic manifestations termed
hyponatremic encephalopathy, ranging from
 Mild nonspecific symptoms (e.g., headache, nausea) to
 More significant disorders (e.g., disorientation, confusion,
obtundation, focal neurologic deficits, and seizures.
 Clinical manifestations also depend on whether the
Hyponatremia is of Acute or Chronic onset

16.  Treatment Of SIADH :
3 components to the treatment of hyponatremia in
SIADH:
●Treatment of the underlying disease, if possible
●Initial therapy to raise the serum sodium
●Prolonged therapy in patients with persistent SIADH
 A variety of causes of SIADH can be effectively
treated, leading to resolution of the hyponatremia.
These include:
 Hormone replacement in adrenal insufficiency or
hypothyroidism
 Treatment of infections such as meningitis,
pneumonia, or tuberculosis
 Cessation of offending drugs, such as selective
serotonin reuptake inhibitors or chlorpropamide

17.  Initial therapy to raise the serum sodium
 Fluid restriction — is a mainstay of therapy in most
patients with SIADH, with a suggested goal intake of less
than 800 mL/day .
 The associated negative water balance initially raises the
serum sodium concentration toward normal and, with
maintenance therapy in chronic SIADH, prevents a further
reduction in serum sodium.
 Intravenous saline — Severe, symptomatic, or resistant
hyponatremia in patients with SIADH often requires the
administration of sodium chloride.
 If the serum sodium concentration is to be elevated, the
electrolyte concentration of the fluid given must exceed
the electrolyte concentration of the urine, not simply
that of the plasma

18.  Principles of Correction of Hyponatremia with IV saline
 Aggressive treatment of hyponatremia has a risk of
inducing CMP which is a rare but serious
complication
 Develops one to several days after aggressive
treatment of hyponatremia- which is indicated in
patients with severe symptoms such as seizures,
stupor, coma, and respiratory arrest, regardless of the
degree of hyponatremia.
 The goal is to correct hyponatremia at a rate that
does not cause neurologic complications.
 Raise serum Na+ levels by 0.5-1 mEq/h, and not more
than 10-12 mEq / 24 hours, to bring the Na+ value to
a level of 125 -130 mEq/L.

19.  Approximate Na+ deficit -(0.5 L/kg for females):
 Na+ Deficit (mEq) =(Desired Na+ - MeasuredNa+)
x 0.6 L/kg x Weight (kg)
 3% hypertonic saline has 513 mEq/L each of Na+ and
Cl- and has an osmolality of 1026 mOsm/L. The
volume of hypertonic saline needed to correct that
deficit can be calculated as follows:
 Volume of 3% Saline = (Na+ Deficit)/513 mEq/L
Na+

20.  Assuming a rate of correction of chronic
hyponatremia of 0.5 mEq/L per hour, the amount of
time needed to correct a given degree of
hyponatremia is as follows:
 Time Needed for Correction = (Desired Na+ -
Measured Na+)/0.5 mEq/L per hour
 The rate of infusion of hypertonic saline is as
follows:
 Rate = (Volume of 3% Saline)/(Time Needed for
Correction)

21.  Loop Diuretic like Furosemide increases excretion
of free water and has been used along with
hypertonic saline in severe cases to limit treatment-
induced volume expansion. The diuresis induced by
furosemide has a urine solute concentration roughly
equivalent to half-normal saline
 Oral Salt Tablets can also be administered to correct
chronic hyponatremia

22.  The vasopressin receptor antagonists –
( V2 Receptor antagonists) produce a selective water
diuresis (aquaresis) without affecting sodium and
potassium excretion .
 (Inhibition of the AVP V2 receptor reduces the
number of aquaporin-2 water channels in the renal
collecting duct and decreases the water permeability
of the collecting duct.)
 The ensuing loss of electrolyte-free water will tend to
raise the serum sodium in patients with SIADH

23.  2 aquaretics approved by FDA.
 Conivaptan is a parenteral nonpeptide dual AVP V1a- and
V2-receptor antagonist, which is approved for use in
hospitalized patients with euvolemic (dilutional) and
hypervolemic hyponatremia.
 The drug is given as a 20-mg loading dose followed by a
continuous infusion or as intermittent boluses, but it should
not be used for more than 4 days.
 Tolvaptan is a selective oral V2 receptor antagonist also
approved for use in hospitalized patients for hypervolemia
and euvolemic hyponatremia.
 The drug is started at 15 mg once daily and titrated up to 60
mg daily as required, and it is best to avoid fluid restriction
during the dose-finding phase

24.  Tolvaptan should not be used for longer than 30 days and should
not be given to patients with liver disease (including cirrhosis)
 There may be overly rapid correction of the hyponatremia, which
can lead to irreversible neurologic injury.
 Thirst is increased, which may limit the rise in serum sodium
 They can be used in conjunction with hypertonic saline
and Fluid restriction to correct resistant Hyponatremia
 Demeclocycline is a tetracycline derivative that induces
diabetes insipidus by impairing the generation and action of
cAMP, thus interfering with the action of AVP on the
collecting duct.
 The drug's onset of action may be delayed by over a week;
thus, it is not indicated for the emergency management of
symptomatic hyponatremia.

25.  The choice of therapy in patients with hyponatremia due to
SIADH varies with the severity of hyponatremia and the
presence or absence of symptoms.
 severe symptomatic hyponatremia who present with
seizures or other severe neurologic abnormalities or with
symptomatic hyponatremia in patients with intracerebral
diseases, urgent intervention with hypertonic saline is
preferred
 Slow correction with fluid restriction, Added oral salts and
if indicated hypertonic saline is preferred in case of chronic
hyponatremia
 Resistant cases of Hyponatremia use of vaptans along with
above measures can be considered

26.  THANK YOU