Basic concepts

Despite making up only 1% of total body weight, the kidneys receive approximately 25% of the cardiac output.

The volume of plasma filtered by the kidneys is termed the glomerular filtration rate (GFR) and is equal to approximately 180 L/day for a person weighing 70 kg. This means that the entire plasma volume is filtered about 60 times a day. The kidneys have a large functional reserve and the loss of one kidney normally produces no ill-effects. The ureters transport the urine from the kidney to the bladder, where urine is stored. Urine leaves the bladder through the urethra. In women, this is a short tube that opens just in front of the vagina. In men, the tube is longer, passing through the prostate and the penis. The kidneys have the most complex functions (see below), the bladder functions as a storage sac, and the ureter and urethra mainly act as conduits for the transportation of urine.

The kidney

The nephron

Each kidney is made up of approximately one million functional units, known as ‘nephrons’ (Fig. 7.1). Each nephron consists of:

• A renal corpuscle which comprises a glomerulus and a Bowman’s capsule.

• A tubule which comprises a proximal tubule, loop of Henle, distal convoluted tubule and collecting duct system.

Fig. 7.1 Structure of the juxtaglomerular nephron.

(Redrawn from Page et al. 2006.)

(Redrawn from Page et al. 2006.)

Fig. 7.3 Transport mechanism in the thick ascending loop of Henle. Loop diuretics block the Na⁺/K⁺/2Cl^– co-transporter (1) thereby increasing the excretion of Na⁺ and Cl^–. These drugs also decrease the potential difference across the tubule cell, which arises from the recycling of K⁺ (2), and this leads to increased excretion of Ca²⁺ and Mg²⁺ by inhibiting paracellular diffusion (3).

(Redrawn from Page et al. 2006.)

Fig. 7.4 Transport mechanisms in the early distal tubule. Thiazide diuretics increase the excretion of Na⁺ and Cl^– by inhibiting the Na⁺/Cl^– co-transporter (1). The reabsorption of Ca²⁺ (2) is increased by these drugs by a mechanism that may involve stimulation of Na⁺/Ca²⁺ countertransport (3) due to an increase in the concentration gradient for Na⁺ across the basolateral membrane.

(Redrawn from Page et al. 2006.)

Fig. 7.5 Transport mechanisms in the late distal tubule and collecting duct. Amiloride and triamterene block the luminal Na⁺ channels, which reduces the lumen-negative potential difference across the principal cell and decreases the driving force for K⁺ secretion from the principal cell and H⁺ secretion from the intercalated cell. The net effect is increased Na⁺ excretion and decreased K⁺ and H⁺ excretion. Aldosterone binds to a cytoplasmic mineralocorticoid receptor (MR) stimulating the production of aldosterone-induced proteins (AIP), which (1) activate and increase the synthesis of Na⁺ and K⁺ channels; (2) increase the synthesis of Na⁺/K⁺ ATPase, and (3) increase mitochondrial production of adenosine triphosphate (ATP). The effect of aldosterone is to decrease Na⁺ excretion and increase K⁺ and H⁺ excretion in urine, whereas spironolactone, an aldosterone antagonist, has the opposite effects.

(Redrawn from Page et al. 2006.)

Water is reabsorbed by passive diffusion, following the movement of sodium ions, and through specific water channels (aquaporins) in the collecting tubules, which greatly increases the reabsorption of water.

Proximal tubule

The Bowman’s capsule extends into the proximal tubule, which is made up of an initial convoluted section and a straight section. The proximal tubule is permeable to water and ions and is the site into which many drugs are secreted. Approximately two-thirds of the filtrate volume is reabsorbed back into the blood in the proximal tubule.

Sodium movement into the cell is coupled with that of glucose and amino acids, whereas chloride movement is by passive diffusion (Fig. 7.2). Reabsorption of bicarbonate also takes place in the proximal tubule.

Loop of Henle

The loop of Henle consists of a descending limb, a thin ascending limb and a thick ascending limb.

Twenty-five per cent of filtered sodium is reabsorbed in the thick ascending limb (see Fig. 7.3), but this portion of the tubule is impermeable to water. Increase in the solute load (sodium) in the interstitium between the ascending loop and the collecting tubules sets up an osmotic gradient which subsequently permits water reabsorption from the collecting tubules – the countercurrent multiplier system.