All of the following statements regarding ADH (vasopressin) and water balance are correct EXCEPT:

## Mechanism of ADH Action **Key Point:** ADH (vasopressin) acts primarily on the **collecting duct**, not the proximal convoluted tubule. The proximal tubule is already constitutively permeable to water and reabsorbs ~65% of filtered water regardless of ADH status. ### Sites of ADH Action | Structure | ADH Sensitivity | Effect | |-----------|-----------------|--------| | Proximal Convoluted Tubule | Insensitive (constitutively permeable) | Obligatory water reabsorption (~65%) | | Loop of Henle | Insensitive | Water reabsorption in descending limb only | | Collecting Duct | Highly sensitive (V2 receptors) | Regulated water reabsorption via aquaporin-2 | | Vasa Recta | V1 receptors present | Vasoconstriction (minor role) | ### Correct Statements About ADH **Statement 1 — TRUE:** - ADH is synthesized in the **supraoptic and paraventricular nuclei** of the hypothalamus [cite:Guyton Ch 28] - Stored in the posterior pituitary and released in response to osmotic and baroreceptor signals **Statement 2 — TRUE:** - ADH binds **V2 receptors** on the basolateral membrane of collecting duct principal cells - Activates cAMP → increases expression and insertion of **aquaporin-2 (AQP2)** water channels into the apical membrane - This is the **primary mechanism** of regulated water reabsorption **Statement 3 — TRUE:** - ADH secretion is **inhibited** when plasma osmolality falls below **280 mOsm/kg** - This is the osmotic threshold for ADH suppression - Below this threshold, the collecting duct becomes impermeable to water, allowing excretion of dilute urine **Statement 4 — FALSE:** - ADH does **NOT** increase permeability of the proximal convoluted tubule - The proximal tubule is already maximally permeable to water due to constitutive aquaporin-1 channels - ADH action on the collecting duct is the **fine-tuning mechanism** for water balance ## Clinical Pearl **High-Yield:** In **diabetes insipidus**, the problem is either: 1. **Central DI:** Lack of ADH synthesis/release → collecting duct remains impermeable → polyuria + polydipsia 2. **Nephrogenic DI:** Collecting duct resistance to ADH (V2 receptor defect or aquaporin-2 defect) → same clinical picture The proximal tubule's water reabsorption continues normally in both cases, but the collecting duct cannot respond. ## Mnemonic **ADH Action Sites (PCLD):** - **P**roximal = Insensitive (always permeable) - **C**ollecting duct = Sensitive (regulated by ADH) - **L**oop of Henle = Insensitive (descending limb only) - **D**istal convoluted tubule = Minimally sensitive