| 1. Failure of diuretics to reach tubular site of action |
| - Decreased G.I. absorption ( Gastro Intestinal edema) |
| - Decreased secretion into tubular lumen (↓ GFR) |
| 2. Compensatory Mechanisms |
| - RAAS, SNS ↑Na reabsorption in PCT |
| 3. Post dose Compensatory retention of Na |
| 4. Tubular adaptation |
| - Chronic Loop diuretic use- RAAS stimulation leading to Hypertrophy and hyperplasia of DCT |
| 5. ↑Aldosterone in CD |