Diabetes Insipidus: Pathogenesis and clinical findings
Hereditary
Autoimmune/ Idiopathic
Auto-antibodies destroy neurons that release antidiuretic hormone (ADH)
Mass Effect/ Tumor Invasion
Mass pressing on hypothalamus or pituitary
Electrolyte Imbalance
(mechanism unclear)
Hereditary
Lithium (Li)
(mechanism unclear)
Li enters principal cells of collecting ducts via ENaCs
Li inhibits GSK3β, reducing adenylyl cyclase activity
↓ cAMP- dependent phosphorylation of aquaporin-2
↑ Serum [Ca2+]
Activation of
CaSR in thick ascending limb of Loop of Henle
↓ NaCl reabsorption in thick ascending limb
↓ Generation of medullary osmotic gradient
↓ Serum [K+]
↑ Degradation of aquaporin-2 channels in collecting duct
↓ Aquaporin- 2 channels transporting water across apical membrane of collecting duct
Mutation of AVPR2 gene on X chromosome
Antidiuretic hormone (ADH) receptor cannot reach basolateral surface of principal cells of collecting duct
Mutation of aquaporin-2 gene on chromosome 12
↓ Fusion of aquaporins with apical membrane of collecting duct
Mutation of WFS1 gene on chromosome 4 (Wolfram syndrome)
↓ Processing of antidiuretic hormone (ADH) precursors and ↓ADH-releasing neurons
Surgery/ Trauma
Injury to hypothalamus or pituitary stalk
Mutation of PCSK1 gene on chromosome 5
Deficiency in PC1/3 (encoded by PCSK1)
↓ Processing of ADH by PC1/3
Aquaporin dysfunction
↓ Kidney response to ADH, which mediates reabsorption of water down its osmotic gradient through aquaporins
↓ Production of ADH by hypothalamus or ↓ secretion from ADH-releasing neurons in posterior pituitary (depending on location of lesion)
Central Diabetes Insipidus
Nephrogenic Diabetes Insipidus
Abbreviations:
AVPR2: arginine vasopressin receptor 2 CaSR: calcium-sensing receptor
ENaC: epithelial sodium channel
GSK3β: glycogen synthase kinase type 3 beta PC1/3: proprotein convertase
Diabetes Insipidus
Decreased ability of kidneys to concentrate urine
↓ Reabsorption of water from collecting duct into vasculature
Author:
Oswald Chen
Reviewers:
Huneza Nadeem,
Ran (Marissa) Zhang,
Yan Yu*
Sam Fineblit*
* MD at time of publication
Urine becomes more dilute
↓ Urine osmolality
↑ Urine output
↓ Blood volume
Blood becomes more concentrated
Occurs during late sleep period
Nocturia
Polyuria
(>3 L/day)
↑ Serum osmolality
Activation of hypothalamic osmoreceptors
Hypernatremia
(Serum [Na+] >145 mEq/L)
Polydipsia
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published September 25, 2022 on www.thecalgaryguide.com