CAPT SAFIA FATIMA

AFIP

Terminology
Osmolality = No. of solute particles/ Kg
H2O
Temperature independent
Osmolality=2(Na) +urea +glucose
The osmolality of the ECF is normally maintained

in the range 282-295 mmol/kg of water

Osmolarity = No. of solute particles/ L

H2O
Osmolarity is not commonly used because it is

temperature dependent. This is because water

changes its volume with temperature

Osmolal Gap
Osmolal gap = measured plasma osmolality calc plasma
osmolality
Causes of inc osmolal gap ( > 10 mosm/kg ):
Presence of non electrolyte solute other than glucose or
urea.
Significant discrepancies, when the fractional water content
of
plasma is reduced
Hyperlipdaemia
Hyperproteinaemia

Water Distribution

Approximately 66% of this water is in the intracellular fluid (ICF) and

33% in the extracellular fluid (ECF); only 8% of body water is in the

Distribution Of Water
Total body water
Anatomical ECW
Transcellullar

Intracellular

Physiological
Plasma

Interstitial Fluid

Anatomical ECW includes water external to the cell

membranes through which all metabolic exchange occurs
Physiological ECW is the portion of anatomical ECW whose
volume is accessible to direct measurement

Water Intake & Loss

Water Regulation
ECF osmolality
Vasopressin (ADH)
Hypothalamic thirst centre
ECF volume

Water Regulation
If ECF osmolality falls, there is no sensation of

thirst and vasopressin secretion is inhibited. A

dilute urine is produced, allowing water loss
and restoration of ECF osmolality to normal.

Hormonal Regulation of
Blood Volume

Causes Of Water Depletion

And Clinical Features

Water Deficiency
Water deficiency may manifest in four forms
Pure water depletion
Isotonic fluid loss
Hypotonic fluid loss
Hypertonic fluid loss

16

Water Deficiency
PURE WATER DEPLETION;Body water loss without sodium loss
Uncommon,Patient too old or too young or too sick to drink
Disturbance of thirst center

Neurogenic,Psychogenic

Hypovolemia,Clinically , may be euvolaemic

High conc. urine (Oliguria)
Urinary Na+ decrease

17

Water Deficiency
ISOTONIC FLUID LOSS
Sodium and water loss in the ratio of 140 mmol of Na + for every

liter of pure water e.g;

Blood loss
Serum loss, burns
Third space accumulation e.g. ileus, pancreatitis, peritonitis,
crush injury
No change in ECF osmolality
No shift of fluid b/w ICF and ECF
Decreased ECF volume
Hypotension
18

Water Deficiency
HYPOTONIC FLUID LOSS
Na+ is lost in excess of water

Excessive sweating
Vomiting, diarrhea, drainage into fistula
Addisons disease
Diuretic therapy
Salt losing nephritis
Diabetes insipidus

Gross decrease in ECF volume

19

Overhydration
Increase in total body water with normal total body

sodium
It results from excessive water consumption
(polydipsia)
Water intoxication results from imapaired renal free
water excretion as a result of ADH secretion
Excess ADH is known as SIADH(syndrome of
inappropriate ADH secretion)
Water intoxication dilutional hyponatremia &
hyposmolarity of ECW results in water movement into
the cells
Symptoms of water intoxication are related to rate of
fall in sodium

Causes Of Water Excess

And Clinical Features

Consequences
Oedema
Hyponatraemia
Cerebral oedema
Low conc. of other blood analytes
Low ECF osmolality
Intracellular fluid shift
Intracellular oedema

22

Arginine Vasopressin (AVP)

Vasopressin is synthesized by the supraoptic and

paraventricular nuclei of the hypothalamus

It is then transported to the posterior pituitary
and stored.
Vasopressin release from posterior pituitary is
primarily regulated by changes in plasma
osmolality
The primary site of vasopressin action in the
kidney is at the collecting duct
Vasopressin receptors are classified as V1 and V2

Arginine Vasopressin
It is also known as ADH,Vasopressin.
REGULATION OF SECRETION
1.Osmoreceptor mechanism
2.Pressure volume mechanism
3.Regulation by thirst centre

24

Arginine Vasopressin
OSMORECEPTOR MECHANISM
Osmolality of the blood is the main regulator of

AVP secretion
As little as a 2% increase in ECF osmolality

causes shrinkage of osmoreceptor cells with

stimulation of AVP release from the posterior
pituitary lobe
A plasma osmolality above 280 mOsm/kg is

considered the osmotic threshold for AVP release

25

Arginine Vasopressin
PRESSURE VOLUME MECHANISM
AVP is regulated by baroreceptors that respond to

alterations in the blood volume. A reduction in

plasma volume or arterial pressure, or both,
stimulate AVP secretion
Non-osmotic stimuli for AVP release include pain,

stress, sleep, exercise and chemical agents such as

catecholamines,
angiotension
II,
opiates,
prostaglandins,
anaesthetics,
nicotine
and
barbiturates
Alcohol, phenytoin, and glucocorticoids inhibit AVP

release

26

Arginine Vasopressin
THIRST CENTRE

This centre has a higher set-point than the

osmoreceptors and respond to osmolalities above

290 mOsm/kg
Responses involving AVP, thirst, and the kidney

are coordinated together to maintain plasma

osmolality within a narrow range of 284 to 295
mOsm/kg
27

Arginine Vasopressin
PHYSIOLOGICAL ACTIONS
Controls water homeostasis which allows the

kidney to reabsorb water and concentrate urine

Generalized vasoconstriction that leads to a rise
in arterial blood pressure
Maintains blood pressure during blood loss
Release of AVP into pituitary portal system
augments the action of CRH in stimulating the
release of ACTH from the adenohypophysis
Exerts contractile influence on the uterus
Promotes contraction of intestinal musculature
28

The vasopressin response to a fall in blood pressure is exponential: it is

relatively small with small decreases in plasma volume, but greater falls
cause a massive increase in vasopressin secretion

Disorders Of ADH Activity

ADH- DEFICIENCY
Deficient production or action of AVP results in

polyuria caused by the failure of the renal

tubules to reabsorb solute-free water
When
urine
output
is
>2.5L/day,
an
investigation is usually indicated as urine output
may approach 1L/hr in complete deficiency of
AVP
Polyuric states is known as diabetes incipidus.

31

Definition
Diabetes insipidus (DI) is a disease

characterized by polyuria and polydipsia

due to decrease secretion or action of
antidiuretic hormone (ADH)

Types Of Diabetes Insipidus

Neurogenic- also called central or pituitary, it is

caused by a deficiency of the antidiuretic

hormone, vasopressin.

Nephrogenic-

caused by a defect in the

receptor to the hormone, vasopressin, located
in the kidneys.

Gestagenic- caused by a deficiency of the

antidiuretic
pregnancy.

Dipsogenic-

hormone,

vasopressin,

during

form of primary polydipsia,

abnormal thirst and excessive intake of liquids.

Hypothalamic
Insipidus

Diabetes

Also called as neurogenic, cranial, or central DI

It is caused by failure of pituitary gland to secrete
normal amounts of AVP in response to
osmoregulatory factors
Other causes include:

Neoplastic diseases
Neurological surgery
Head trauma
Ischemic or hypoxic disorders
Granulomatous diseases
Infections
Autoimmune diseases

34

Contd
In the newborn, DI has been reported in

association with asphyxia, IVH, intravascular

coagulopathy, Listeria monocytogenes sepsis,
and bacterial meningitis and encephalitis.
Approx 20% of cases of DI are idiopathic

Nephrogenic Diabetes Insipidus

It results from the failure of kidney to respond to normal

or increased concentrations of AVP
Primary inherited causes;The cause may be the
incapability of AVP to stimulate cAMP formation. Mutation
in the AVP receptor and mutations in the aquaporin-2
water channels are thought be responsible
Acquired forms: of NDI may be causes by:
Metabolic disorders (hypokalemia, hypercalcaemia,
amyloidosis)
Drugs (lithium, demeclocycline, and barbiturates)
Renal diseases ( polycystic disease and chronic renal
failure)
idiopathic.
36

Clinical Manifestations
POLYURIA, chronic passage of large volumes of urine
POLYDIPSIA, chronic, excessive thirst
OTHER
fever
irritability
constipation
failure to thrive
lack of appetite
vomiting
high blood levels of sodium

Contd
Neurogenic DI
Hypothalamic tumors: growth

disturbances, progressive cachexia or

obesity, hyperpyrexia, sleep
disturbance, sexual precocity, or
emotional disorders
Lesions initially causing DI may
eventually destroy the anterior pituitary
and its associated endocrine axis

Patient History
How much fluid intake per day
Voiding patterns
Dietary intake
Drug history

Laboratory investigations
Urine is usually pale and colorless
Urine analysis and urine electrolytes
Urine specific gravity varies b/w 1.001 and

1.010
Urine osmolality 50-300 mosm/kg
Serum osmolality may vary widely,
depending on hydration status
Other renal function studies usually normal
Serum vasopressin measurement

Polyuria

Measure:
Blood glucose
Creatinine
Potassium
Calcium

abnormal

diagnosis

normal
Fluid deprivation
test

Urine osmolality (mmol/kg) after:

8 h fluid deprivation

desmopressin

< 300

>600

neurogenic DI

<300

<300

Nephrogenic DI

>600

>600

Primary polydipsia

300-600

<600

Non-diagnostic

Diagnosis

Water deprivation test

In patients with severe neurogenic DI,

overnight water deprivation results in

elevation
of
Serum
and
urine
osmolality after administration of
vasopressin.
In nephrogenic DI there is no effect on
serum & urine osmolality after
administration of desmopressin.

Diagnosis
Administration of desmopressin
In neurogenic DI, desmopressin will raise
Urine osmolality& suppress urine out put.
In nephrogenic DI, desmopressin produces no
increase in Urine osmolality and no
suppression of Urinary out put.
In normal individuals, desmopressin
administration can cause a vasodilatory
response (flushing, fall in diastolic BP, rise in
HR), believed to be mediated by extra renal
V2 receptors

Treatment

neurogenic DI
Administration of desmopressin, usually
intranasal.
Desmopressin binds almost exclusively to V2
receptors and is more resistant to degradation by
body peptidases than endogenous vasopressin
Therefore, the antidiuretic effects of
desmopressin last 8-10 hr, compared with 1-3 hr
for endogenous vasopressin
Dose: 5-10 mcg intranasal, given in single or
divided doses; < 2 y/o: 0.15-0.5 mcg/kg/24 hr
IV/SC therapy also available

Treatment
Nephrogenic DI
Ensure a sufficient intake of water to

replace the large urinary water losses

Stop causative medications, if
applicable
Low sodium diet
Drugs that reduce polyuria
Prostaglandin synthesis inhibitors (indomethacin)
Potassium-sparing diuretics (amiloride)

Management
Check serum electrolytes frequently
After episodes of dehydration, these patients usually

require replacement of large quantities of water, but not

sodium
Neurogenic DI prognosis often determined by the
underlying etiologic process
Nephrogenic DI good prognosis,There are isolated
reports of chronic renal failure

Psychogenic
Polydipsia

Or

Primary

Chronic, excessive intake of water suppresses

AVP secretion and produces hypotonic polyuria
Psychogenic
factors
are
most
commonly
associated with this disorder, but hypothalamic
disease affecting the thirst centre may be a
cause
Drugs can also affect thirst centre and may cause
primary polydipsia

47

Disorders Of AVP Activity

SIADH
It refers to autonomous, sustained production of AVP
in the absence of known stimuli for its release
In this syndrome plasma AVP concentrations are
inappropriately increased relative to a low plasma
osmolality and to a normal or increased plasma
volume (i.e., it occurs under conditions that normally
suppress its secretion)

48

Causes Of SIADH
TUMOURS
CA of bronchus, prostate, pancreas
Brain tumours: glioma, meningioma
BRAIN PATHOLOGY
Tumours: trauma/CVA
Infections: abscess, meningitis, encephalitis
PULMONARY PATHOLOGY
Tumours: bronchial CA
Infections: tuberculosis, pneumonia
Pneumothorax, hydrothorax, positive pressure ventilation
MISCELLANEOUS
Pain (post-op)
Acute intermittent porphyria
GB Syndrome
Hypothyroidism
Drugs: narcotics, carbamazepine, oxytocin

49

Pathophysiology Of SIADH

50

SIADH
FEATURES
The characteristic features are:
Hyposmolar plasma ( < 270 mOsm/kg)
Urine osmolality slightly greater than that of
plasma
Inappropriately
elevated
urinary
sodium
concentration (40 to 80 mmol/L)
A number of conditions must be satisfied before
making the diagnosis of SIADH. This is to
differentiate it from other causes of hyponatremia
like dilutional and depletional hyponatremia
51

SIADH
FEATURES
In addition to low serum sodium and osmolality
values, and high urine sodium and osmolality
values, the following must be satisfied:

No evidence of dehydration
No
cardiac,
adrenal,
pituitary,
or
thyroid
dysfunction
No drug or diuretic therapy
Clinical and biochemical response to fluid
restriction

52

SIADH
WATER-LOADING TEST
If the cause for mild hyponatremia remains unclear, a
water-loading test may be performed. This test is
however potentially dangerous in patients with severe
hyponatremia and should not be performed if serum
sodium concentrations are < 130 mmol/L
Patients with SIADH have impaired excretion of the
water load and fail to dilute their urine
Measurements of AVP in plasma are usually not needed
to make a diagnosis of SIADH, but basal values would
be expected to be inappropriately high relative to
plasma osmolality
53

Hypervolemic State :
DESCRIPTION:
Hyperglycemic
states that pulls
water from cells
Fluid loss from
extracellular
space greater
than solute loss
leading to increase
serum osmolality >
295.

CLINICAL
PRESENTATION:
CHF
Cirrhosis
Nephrotic
syndrome
Renal failure

TREATMENT:
Water restriction
Loop diuretic
Restrict dietary
salt
Treat underlying
cause

COMMENTS:

Euvolemic State:
DESCRIPTION:
Decrease in fluids
in both the
intravascular and
interstitial space.

CLINICAL
PRESENTATION:
SIADH
Hypothyroidism
Psychiatric
disorders
Medications

TREATMENT:
Water restriction
Increase dietary salt
Treat SIADH
Correct underlying cause

Normal serum
osmolality (275-295)
Use of Na+ free
solutions that result
in dilution of
extracellular space.
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Hypovolemic State :
DESCRIPTION:
Glucose in isotonic
solution oxidized leading
to cellular swelling.
Loss of solute from
extracellular space
greater than excess of
water resulting in
decrease serum
osmolality (< 275)

CLINICAL
PRESENTATION
GI fluid loss
Diuretics
Adrenal insufficiency
Burns
Sweating
Hypotonic
Dehydration

TREATMENT:
IV Normal Saline to correct
the extracellular fluid deficit
*Increase daily salt intake
*Hypertonic saline solution
to increase Na+ levels

Thank You