DIABETES INSIPIDUS

UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE
IM BUNTHOEUN
2017
 OBJECTIVES

- Describe the physiological effects of ADH

- Describe clinical presentation of diabetes insipidus

- Describe etiology of diabetes insipidus

- Explain pathogenesis of diabetes insipidus

- Describe clinical manifestations of diabetes insipidus

 Osmoreceptor
Osmotic pressure
Hypothalamic

Posterior pituitary

ADH

Kidneys (V2 receptor)

Water reabsorption
distal tubule
> 10 liters / day
Collecting duct
Barroreceptor • Hemorrhage
• Blood pressure

Hypothalamus

Blood pressure
ADH

Blood vessel
V1receptor Vasoconstriction
 CLINICAL PRESENTATION

- Polyuria and accompanied by thirst.

- No further symptoms develop if the patient is able to

maintain a water intake commensurate with the water
loss.

- The urine output in the total absence of vasopressin may

reach10-20L/d
 ETIOLOGY

- Central diabetes insipidus (central nervous system):

affecting the synthesis or secretion of vasopressin

- Nephrogenic diabetes insipidus (disease of the kidneys)

- Pregnancy with probable increase metabolic of

clearance of vasopressin
 II- ETIOLOGY

A. Central diabetes insipidus

- Hereditary, familial
- Mutation in the vasopressin gene(autosomal dominant)
- Acquired:
• Idiopathic, traumatic or postsurgical,
• neoplastic disease,
• ischemic or hypoxic disorder, infections: viral
encephalitis,
• bacterial meningitis, and autoimmune disorder
 ETIOLOGY

B. Nephrogenic diabetes insipidus:

- Hereditary, familial
- Mutation in the vasopressin type 2 receptor gene (X-
linked recessive)
- Mutation in the aquaporin 2 gene
- Acquired:
• Hypokalemia, Hypercalcemia
• Postrenal obstruction
• Drugs: lithium and other salts.
• Sickle cell trait or disease, pregnancy
 PATHOPHYSIOLOGY

A. Central diabetes insipidus

- Permanent or, transient, reflecting the neural history
of the underlying disorder

- Permanent DI: destruction of the hypothalamus or

the higher supraotic hypophysial tract must also
occur
- A more common finding is transient disease: acute
injury with neuronal shock and edema
 PATHOPHYSIOLOGY

B. Nephrogenic diabetes insipidus

- Familial nephrogenic DI: defect in the V2 class of
vasopressin receptors
- V1 class receptors unimpaired
- Drug induced nephrogenic diabetes insipidus due
to a sensitivity of the vasopressin receptor to
lithium, fluoride and other salts (12-30%)
 PATHOPHYSIOLOGY

C. Pregnancy
– Excessive vasopressinase in plasma
– Its level falls after delivery
 CLINICAL MANIFESTATIONS

• DI must be distinguished from other causes of polyuria

and hypernatremia
– Diabetes insipidus: dilute urine and hypernatremia

– Osmotic diuresis: high urine osmolality

– Primary polydipsia: hyponatremia

 CLINICAL MANIFESTATIONS

• Usually an acute onset

- In neurogenic DI: three phase syndrome:
• Initailly, significant diuresis,
– as a result of acute damage to the hypothalamic
centers involving ADH secretion (4-5d)

• The second phase: is one of antidiuresis,

– due to necrosis of denervated tissue of the
posterior pituitary with release ADH into the
circulation (5-6d)
 CLINICAL MANIFESTATIONS

• Usually an acute onset

– In neurogenic DI: three phase syndrome:
• The final phase is one of polyuria
–and polydipsia reflecting a permanent loss
of the ability to secrete adequate amount of
ADH.
 CLINICAL MANIFESTATIONS

• Dehydration with consequent hypernatremia:

neurologic manifestation

– progressive obtundation (decreased

responsiveness to verbal and physical stimuli)

– myoclonus, seizures, focal deficits, and coma

 Major Causes Of Hypernatremia

1 IMPAIRED THIRST 3 SOLUTE DIURESIS

Coma, essential hypernatremia
2 EXCESSIVE WATER LOSS
Central diabetes insipidus,
Nephrogenic diabetes insipidus
Sweating
Osmotic diarrhea, and burns
Diabetic ketoacidosis
Nonketotic hyperosmolar coma
Manitol administration
4 SODIUM EXCESS
Administration of hypertonic NaCl
Administration of hypotonic
NaHCO3
 CLINICAL MANIFESTATIONS

• The time course of hypernatremia is an important

variable in the development of neurologic symptoms
– neurones generate “ idiogenic osmoles” amino
acids and other metabolites to raise intracellular
osmolality to the level in the blood and minimize
fluid shifts out of the cells of the brain.
 CLINICAL MANIFESTATIONS

• Distinguishing central from nephrogenic diabetes:

- Determination of responsiveness to injected
vasopressine

- Nephrogenic diabetes insipidus: decrease urine

volume and increase in urine osmolality
 Posterior
Hypothalamus Kidneys
Pituitary

Central diabetes Nephrogenic

Level of ADH
insipidus diabetes insipidus

• Concentrate urine Level of ADH

Polydipsia • Conserve urine

Hypotonic Polyuria

Urine osmolality Plasma osmolality

Specific gravity Plasma sodium
Urine sodium
 REFERENCES

• S Silbernagl Florian LANG (2000), Atlas de poche de

physiopathology.
• Stephen J. McPhee et al (2014), Pathophysiology of
disease: an introduction to clinical medicine
• Thomas J. Nowak, et al, 2014. Essentials of
Pathophysiology. Concepts of Altered Health States