664 CHAPTER 17 Basic science in urological practice

Renal physiology: regulation of water balance

Total body water (TBW) is 42 L. It is contained in two major com- partments—the intracellular fluid (ICF or the water inside cells) which accounts for 28 L and the extracellular fluid (ECF or water outside cells) representing 14 L.

ECF is further divided into interstitial fluid (ISF, 11 L), transcellular fluid (1 L), and plasma (3 L). Hydrostatic and osmotic pressures influence movement between the compartments. Water is taken in from fluids, food, and oxidation of food.

Water is lost from urine, feces, and insensible losses. Intake and losses usually balance (~2 L/day) and TBW remains relatively constant.

Antidiuretic hormone (ADH or vasopressin)

ADH is secreted from the posterior pituitary in response to stimuli from changes in plasma osmolarity (detected by osmoreceptors in the hypothalamus) or changes in blood pressure or volume (detected by baroreceptors in the left atrium, aortic arch, and carotid sinus). These changes also stimulate the thirst center in the brain.

The action of ADH on the kidney

•Increases collecting duct permeability to water and urea

•Increases loop of Henle and collecting duct reabsorption of NaCl

•Increases vasoconstriction

Conditions of water excess

Water excess occurs when body fluids become hypotonic and ADH release and thirst are suppressed. In the absence of ADH, the collecting duct is impermeable to water and a large volume of hypotonic urine is produced, thus restoring normal plasma osmolarity.

Conditions of water deficit

When body fluids are hypertonic, ADH secretion and thirst are stimulated. The collecting duct becomes permeable, water is reabsorbed into the lumen, and a small volume of hypertonic urine is excreted.

The ability to concentrate or dilute urine depends on the countercurrent multiplication system in the loop of Henle. Essentially, a medullary concentration gradient is generated (partly by the active transport of NaCl), which provides the osmotic driving force for the reabsorption of water from the lumen of the collecting duct when ADH is present.

Children have a circadian rhythm in ADH secretion—high at night and low during the day. Adults essentially have a constant ADH secretion over a 24-hour period, with slight increases occurring around mealtimes. At these times, increased ADH secretion probably acts to prevent sudden increases in plasma osmolality that would otherwise occur due to ingestion of solutes in a meal.

RENAL PHYSIOLOGY: REGULATION OF NA AND K EXCRETION 665

Renal physiology: regulation of sodium and potassium excretion

Sodium regulation

NaCl is the main determinant of ECF osmolality and volume. Osmolality = osmoles per kg water (osmol/kg). Osmolarity = osmoles per liter of solution (osmol/L.

Low-pressure receptors in the pulmonary vasculature and cardiac atria, and high-pressure baroreceptors in the aortic arch and carotid sinus recognize changes in the circulating volume. Decreased blood volume triggers increased sympathetic nerve activity and stimulates ADH secretion, which results in reduced NaCl excretion.

Conversely, when blood volumes are increased, sympathetic activity and ADH secretion are suppressed, and NaCl excretion is enhanced (natriuresis).

A variety of natriuretic peptides have been isolated that cause a natriuresis. Under physiological conditions, renal natriuretic peptide (urodilatin) is the most important of these. Atrial natriuretic hormone (ANP) may influence sodium output under conditions of heart failure.

Renin–angiotensin–aldosterone system

Renin is an enzyme made and stored in the juxtaglomerular cells found in the walls of the afferent arteriole. Factors increasing renin secretion are as follows:

•Reduced perfusion of the afferent arteriole

•Sympathetic nerve activity

•Reduced Na+ delivery to the macula densa

Renin acts on angiotensin to create angiotensin I. This is converted to angiotensin II in the lungs by angiotensin-converting enzyme (ACE). Angiotensin II performs several functions, which result in the retention of salt and water:

•Stimulates aldosterone secretion (resulting in NaCl reabsorption)

•Vasoconstriction of arterioles

•Stimulates ADH secretion and thirst

•Enhances NaCl reabsorption by the proximal tubule

Potassium regulation

K+ is critical for many cell functions. A large concentration gradient across cell membranes is maintained by the Na+-K+-ATPase pump. Insulin and adrenaline also promotes cellular uptake of K+.

The kidney excretes up to 95% of K+ ingested in the diet. The distal tubule and collecting duct are able to both reabsorb and secrete K+. Factors promoting K+ secretion include the following:

•Increased dietary K+ (driven by the electrochemical gradient)

•Aldosterone

•Increased rate of flow of tubular fluid (i.e., diuretics)

•Metabolic alkalosis (acidosis exerts the opposite effect)

Figure 17.2 Diagram showing bicarbonate reabsorption in the proximal convoluted tubule.

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