McKenna's Pharmacology for Nursing, 2e

C H A P T E R 5 0 Introduction to the kidneys and the urinary tract 799

Calcium regulation Calcium is important in muscle function, blood clotting, bone formation, contraction of cell membranes and muscle movement, and is another important cation that is regulated by the kidneys. The absorption of calcium from the gastrointestinal (GI) tract is regulated by vitamin D ingested as part of the diet. The vitamin then must be activated in the kidneys to a form that will promote calcium absorption. Once absorbed from the GI tract, calcium levels are maintained within a very tight range by the activity of parathyroid hormone (PTH) and calcitonin. Calcium is filtered at the glomerulus and mostly reabsorbed in the proximal convoluted tubule and ascending loop of Henle. Fine-tuning of calcium reab- sorption occurs in the distal convoluted tubule, where the presence of PTH stimulates reabsorption of calcium to increase serum calcium levels when they are low (see Figure 50.3 and Chapter 37). Blood pressure control The fragile nephrons require a constant supply of blood and are equipped with a system to ensure that they are perfused. This mechanism, called the renin– angiotensin–aldosterone system , involves a total body reaction to decreased blood flow to the nephrons. Whenever blood flow or oxygenation to the nephron is decreased (due to haemorrhage, shock, heart failure or hypotension), renin is released from the juxtaglomerular cells. (These cells, which are positioned next to the glomerulus, are stimulated by decreased stretch and decreased oxygen levels.) The released renin is imme- diately absorbed into the capillary system and enters circulation. The released renin activates angiotensinogen, a sub- strate produced in the liver, which becomes angiotensin I. Angiotensin I is then converted into angiotensin II by a converting enzyme found in the lungs and some blood vessels. Angiotensin II is a very powerful vasoconstric- tor, reacting with angiotensin II–receptor sites in blood vessels to cause vasoconstriction. This powerful vaso- constriction raises blood pressure and should increase blood flow to the kidneys. Angiotensin II is converted in the adrenal gland to angiotensin III, which stimulates the release of aldos- terone from the adrenal gland. Aldosterone acts on the renal tubules to retain sodium and therefore water. This increases blood volume and further increases blood pressure, which should increase blood flow to the kidneys. The osmotic centre in the brain senses the increased sodium levels and releases ADH, leading to a further retention of water and a further increase in blood volume and pressure, which should again increase blood flow to the kidneys.

The renin–angiotensin–aldosterone system con- stantly works to maintain blood flow to the kidneys. For example, an individual rising from a lying position experiences a drop in blood flow to the kidneys as blood pools in the legs because of gravity. This causes a massive release of renin and activation of this system to ensure that blood pressure is maintained and the kidneys are perfused. Blood loss from injury or during surgery also activates this system to increase blood flow through the kidneys. Drugs that interfere with any aspect of this system will cause a reflex response. For instance, taking a drug such as a diuretic to decrease fluid volume can lead to decreased blood flow to the kidneys as blood volume drops. This in turn leads to rebound retention of fluid as part of the effects of the renin–angiotensin–aldosterone system (Figure 50.4). Regulation of red blood cell production Whenever blood flow or oxygenation to the nephron is decreased (due to haemorrhage, shock, heart failure or hypotension), the hormone erythropoietin is also released from the juxtaglomerular cells. This hormone stimulates the bone marrow to increase the production of red blood cells, which bring oxygen to the kidneys. Erythropoietin is the only known factor that can regulate the rate of red blood cell production. When

↓ Blood flow ↓ Oxygenation

NEPHRON

↑ RBC production

Renin release

Erythropoietin release

Angiotensin I

Activation of angiotensinogen

LUNGS

Converting enzyme (ACE) Angiotensin I Angiotensin II

ADRENAL GLAND Angiotensin III

Powerful vasoconstriction

↑ Aldosterone release

↑ Blood pressure ↑ Blood flow to the kidneys

Retention of sodium with water

↑ Blood volume and pressure ↑ Blood flow to the kidneys

FIGURE 50.4  The renin–angiotensin–aldosterone system for reflex maintenance of blood pressure control.