Physiology
Renal
Regarding the distal nephron, which of the following statements is CORRECT:
Answer:
Na+ is reabsorbed in principal cells via the Na+ channel ENaC which is inhibited by atrial natriuretic peptide (ANP) which therefore acts to decrease Na+ reabsorption in the distal nephron. About 7% of filtered NaCl and about 8 - 17% of water is reabsorbed in the distal tubule and collecting duct. The distal tubule and cortical collecting duct are impermeable to water except in the presence of antidiuretic hormone (ADH), which causes water channels (aquaporins) to insert into the apical membrane, allowing reabsorption, not secretion, of water. K+ secretion is increased by aldosterone which enhances Na+ pump activity and apical membrane K+ permeability.Distal Collecting System
Physiology / Renal / Mechanism of Filtration
Last Updated: 21st April 2019
The distal nephron consists of the late distal tubule and the collecting ducts. The distal tubule is functionally similar to the cortical collecting ducts. Both contain principal cells which respond to antidiuretic hormone (ADH) and intercalated cells which secrete H+ ions (involved in acid-base balance).
About 7% of filtered NaCl and about 8 - 17% of water is reabsorbed in the distal tubule and collecting duct.
Water Permeability
Fluid entering the distal tubule is hypotonic. More Na+ is reabsorbed in principal cells via the Na+ channel ENaC which is inhibited by atrial natriuretic peptide (ANP); expression of ENaC and thus Na+ reabsorption is increased by aldosterone. The movement of Na+ through ENaC is charge compensated by the opposite movement (secretion) of K+ through ROMK channels.
The distal tubule and cortical collecting duct are impermeable to water except in the presence of antidiuretic hormone (ADH), which causes water channels (aquaporins) to insert into the apical membrane. In the presence of ADH, water diffuses into the cortical interstitium, and the tubular fluid becomes more concentrated. The fluid differs from plasma as large quantities of Na+, K+, Cl- and HCO3- have been reabsorbed, their place having been taken by urea. This is concentrated as water is reabsorbed, because the distal tubule and cortical collecting duct are impermeable to urea.
The medullary collecting duct also becomes permeable to water in the presence of ADH. Water is reabsorbed due to the high osmolality of the medullary interstitium. Although only 15% of nephrons have loops of Henle that pass deep into the medulla and so contribute to the high medullary osmolality, the collecting ducts of all nephrons pass through the medulla and therefore concentrate urine.
Urea
The medullary collecting duct is relatively permeable to urea, which diffuses down its concentration gradient into the medulla and then into the ascending loop of Henle. Urea is therefore 'trapped' and partially recycled, so maintaining a high concentration and providing ~50% of the osmolality in the medulla. ADH increases the permeability of the medullary collecting duct to urea and hence its reabsorption by activating epithelial uniporters; this further increases the medullary osmolality and allows the production of more concentrated urine.
Potassium
Potassium has been largely reabsorbed by the time the distal tubule is reached, and so excretion is regulated by secretion in the late distal tubule. K+ is actively transported into principal cells by basolateral Na+ pumps and passively secreted via ROMK channels and K+/Cl- cotransport; the former is promoted by the negative luminal charge caused by reabsorption of Na+ through ENaC. Secretion is therefore driven by the concentration gradient between the cytosol and tubular fluid. However, secreted K+ will reduce the gradient unless it is washed away and so K+ excretion is increased as tubular flow increases; diuretics therefore often lead to K+ loss. K+ secretion is increased by aldosterone which enhances Na+ pump activity and apical membrane K+ permeability. Perturbations of K+ homeostasis are often associated with acid-base disorders.
Calcium
Calcium reabsorption in the distal tubule is regulated by parathyroid hormone and activated vitamin D.
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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 |
