Physiology
Renal
Where in the nephron do loop diuretics primarily act:
Answer:
Loop diuretics e.g. furosemide are the most potent diuretics. They inhibit the Na+/K+/2Cl- symporter in the thick ascending limb of the loop of Henle. This binding inhibits sodium, potassium, and chloride reabsorption, causing diuresis with loss of these electrolytes. The transcellular voltage difference falls, and paracellular calcium and magnesium reabsorption are also reduced. Salt reabsorption in the ascending limb normally concentrates the medullary interstitium, and by blocking this process, loop diuretics reduce the ability of the kidney to concentrate urine. Increased sodium delivery to the principal cells in the collecting duct increases potassium secretion in return for sodium reabsorption.Diuretic Therapy
Physiology / Renal / Mechanism of Filtration
Last Updated: 21st April 2019
Loop Diuretics
Loop diuretics e.g. furosemide are the most potent diuretics.
They inhibit the Na+/K+/2Cl- symporter in the thick ascending limb of the loop of Henle. This binding inhibits sodium, potassium, and chloride reabsorption, causing diuresis with loss of these electrolytes. The transcellular voltage difference falls, and paracellular calcium and magnesium reabsorption are also reduced.
Salt reabsorption in the ascending limb normally concentrates the medullary interstitium, and by blocking this process, loop diuretics reduce the ability of the kidney to concentrate urine. Increased sodium delivery to the principal cells in the collecting duct increases potassium secretion in return for sodium reabsorption.
Thiazide Diuretics
Thiazide diuretics e.g. bendroflumethiazide inhibit the apical Na+/Cl- cotransporter in the early distal tubule. More sodium is then delivered to the principal cells of the collecting duct. Some of this excess sodium is exchanged for potassium, causing hypokalaemia. Reduced sodium reabsorption lowers intracellular sodium concentration, promoting basolateral sodium-calcium exchange and therefore calcium reabsorption.
Osmotic Diuretics
Osmotic diuretics e.g. mannitol are filtered in the glomerulus and then cannot be reabsorbed effectively. As the filtrate passes along the nephron, water is reabsorbed and the concentration of the osmotic diuretic rises until its osmotic effect opposes further water reabsorption. Sodium is then reabsorbed without water. Eventually sodium reabsorption is also inhibited because the sodium gradient between filtrate and plasma increases to the point at which sodium leaks back into the lumen.
Potassium-Sparing Diuretics
Aldosterone promotes sodium reabsorption and potassium secretion by increasing transcription of the ENaC channel and the Na+/K+ ATPase. Aldosterone antagonists e.g. spironolactone block aldosterone receptors so reducing Na+ reabsorption and K+ secretion in the distal nephron.
Carbonic Anhydrase Inhibitors
Carbonic anhydrase inhibitors e.g. acetazolamide block the reaction of carbon dioxide and water and so prevent Na+/H+ exchange and bicarbonate reabsorption. The increased bicarbonate levels in the filtrate oppose water reabsorption. Proximal tubule sodium reabsorption is also reduced because it is partly dependent on bicarbonate reabsorption.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
