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diabetes-insipidus-pathogenesis-and-clinical-findings

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