Blood enters the glomerulus of the kidney under pressure. This pressure forces the water and small molecules (e.g. sodium, potassium, glucose) that are present in the blood through the basement membrane of the glomerulus and into the Bowman’s capsule (Figure 26.2). At this stage, the filtered fluid is mainly blood plasma minus largely all the plasma proteins (there is some seepage of these, but not much). Factors such as heavy exercise can increase the amount of protein found in the urine, but a large amount of protein in the urine indicates kidney pathology. The fluid flows from the Bowman’s capsule into the proximal tubule.

All the amino acids and glucose, and a large amount of the sodium, potassium and other salts are reabsorbed in the proximal tubule. The active transport of sodium out of the proximal tubule is controlled by angiotensin II. If this is reduced, by medication such as an ACE inhibitor (see Figure 26.6), the sodium remains in the tubule, and the water stays with it. As a result, the patient urinates more.

The filtered fluid passes from the proximal tubule into the descending part of the loop of Henle, where the osmotic gradient still encourages water to leave the nephron. The fluid is encouraged to leave the descending part of the loop because, in the ascending part – which is aligned directly opposite – an active transport mechanism pulls sodium salts from the loop; water from the descending loop accompanies the salts as the result of osmosis. However, fluid cannot follow the salts from the ascending loop because the wall of the loop is impermeable to water. This is where loop diuretics work, by preventing sodium reabsorption.

More sodium is removed from the tubules by active transport, with yet more water being pulled out by osmosis. Thiazides (Figure 26.5) such as bendroflumethiazide act here.

This is where the final balancing of water and electrolytes takes place, before the fluid is removed from the body. Potassium-sparing diuretics (Figure 26.5) work here, as well as in the distal convoluted tubules. The collecting tubule is normally impermeable to water, but it can become permeable in the presence of antidiuretic hormone (ADH), which is secreted by the pituitary gland (see Chapter 37 ‘Metabolic disorders’, p. 288). As much as 75% of water in the urine can be reabsorbed as it leaves the collecting duct by osmosis. A failure to produce ADH (due to a fault in the posterior pituitary gland) is seen in the condition known as diabetes insipidus, which involves excretion of copious amounts of urine, despite reduced consumption of fluids.

Levels of potassium are reduced in plasma due to loss of potassium in urine, resulting in:

This is why loop diuretics tend to be used for short-term, acute use only. These adverse effects are usually counteracted with potassium supplements or using a combination diuretic with a thiazide diuretic and a potassium-sparing diuretic.

Long-term diuretic therapy is associated with an impairment of glucose tolerance and an increased incidence of non-insulin dependent diabetes mellitus. This is due to insulin resistance in peripheral tissues.

Reversible on ceasing medication.

Diuretics compete with uric acid for excretion from the kidney tubules, which can concentrate uric acid in the plasma. Care should be taken if patients suffer from gout.

Adverse effects are rare, although spironolactone can upset the gastrointestinal tract and cause rashes.

This plant chemical is very similar in structure to aldosterone (Figure 26.4) and is therefore capable of similar pharmacological actions, hence the need to be aware of why Glycyrrhiza spp. can increase blood pressure.

Rebound worsening of angina, myocardial infarction or tachycardia can occur if beta-blockers are suddenly withdrawn. The dose has to be lowered over a 24- to 48-hour period.