Physiology
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Endocrine
A 69 year old man with known small cell lung cancer is sent to ED by his GP after identifying severe hyponatraemia on a recent blood test. Where in the nephron is the likely cause of this abnormality:
Answer:
Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which develops more frequently with small cell lung cancer (SCLC) than with other malignancies. ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. Therefore by increasing water retention, ADH causes dilution of the blood and in turn decreases the concentration of solutes, such as sodium.Antidiuretic Hormone
Physiology / Endocrine / Pituitary Function / Renal / Mechanism of Filtration
Last Updated: 26th July 2024
Extracellular fluid osmolality must be closely regulated as alterations cause the swelling or shrinking of cells and can lead to cell death. Osmoreceptors in the anterior hypothalamus control water intake by altering thirst and control renal water excretion by altering antidiuretic hormone (ADH) release. A rise in osmolality triggers ADH release and stimulates thirst; a fall has the opposite effect.
Synthesis
Antidiuretic hormone is synthesised in the hypothalamus and transported to the posterior pituitary within nerve fibres where it is stored in secretory granules.
Action
ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine.
ADH also binds to V1 receptor receptors on vascular smooth muscle, causing vasoconstriction and enhancing the effect of aldosterone on sodium reabsorption in the distal tubule.
Metabolism
ADH is rapidly removed from plasma, falling by about 50% in about 10 minutes, mainly due to metabolism in the liver and kidneys.
Stimulating Factors
ADH release is stimulated primarily by raised plasma osmolality detected by osmoreceptors in the anterior hypothalamus. Other factors that increase ADH release include: extracellular fluid volume depletion, angiotensin II, nausea, pain, stress, exercise, emotion, hypoglycaemia.
Inhibiting Factors
ADH release is inhibited by low plasma osmolality, alcohol, caffeine, glucocorticoids and atrial natriuretic peptide (ANP).
Clinical Implications
ADH deficiency (or an inadequate response to ADH) results in diabetes insipidus. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH).
Function of Antidiuretic Hormone. (Image by OpenStax College [CC BY 3.0 , via Wikimedia Commons)
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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 |
