On cross-section, the kidney is seen to contain three principal areas: the pelvis, the medulla, and the cortex (Figure 26-2). The renal pelvis is a large collecting area for the urine that drains from the many collecting ducts of the nephrons. The minor (smaller) calices collect urine as it drains from the papilla of the renal pyramids. The normal kidney has 8 to 18 minor calices and 2 to 3 major calices.¹ The major calices are large collecting spaces located between the minor calices and the upper part of the ureter.

The kidneys are innervated by the sympathetic division of the autonomic nervous system. The lesser splanchnic nerves come from the renal plexuses, which are located next to the renal arteries. These nerve fibers travel with the renal arterial blood vessels and terminate in smooth muscle of the afferent and efferent arterioles, proximal and distal tubules, and the renin-secreting juxtaglomerular cells.1,5 Stimulation of the sympathetic nervous system results in renal vasoconstriction and renin release. The renal capsule and all structures between the renal pelvis and urinary meatus are innervated with pain receptors (see Chapter 27).

Approximately 25% of the cardiac output is delivered to the kidneys, the majority of which circulates through the cortex, while only 1% to 2% perfuses the medulla.5 Total renal blood flow in both kidneys is approximately 1250 ml/min. Blood flows to the kidneys from the abdominal aorta through the renal arteries, which then divide into several interlobar arteries.⁵ The interlobar arteries travel in the renal columns adjacent to the pyramids (see Figure 26-2). When the interlobar arteries reach the border of the medulla and the cortex, they branch into the arcuate arteries. The arcuate arteries then travel along the cortical medullary border parallel to the renal capsule. The arcuate arteries branch further to form small interlobular arteries, which penetrate the cortex and branch extensively to form the afferent arterioles. The afferent arterioles divide to form glomerular capillaries, which coalesce to form the efferent arterioles (Figure 26-3). The efferent arterioles branch again to form a second capillary bed. The peritubular capillaries wrap around the proximal and distal convoluted tubules (Figure 26-4). Some capillaries, called vasa recta, dip down into the medulla to surround the loops of Henle and collecting ducts. The vasa recta have a specialized loop structure that enables them to pick up interstitial fluid without excessive removal of interstitial solutes. Solutes and water move into and out of the vasa recta passively such that the descending limb gains solute as it dips into the highly concentrated medulla, but then most of the solute is lost as the ascending loop makes its way back up to the cortex.

The capillaries of the peritubular system and the vasa recta join together and drain into interlobular venules. The veins that drain blood from the kidney run parallel to the arteries and are similarly named (Figure 26-5).

The glomerulus is the site of fluid filtration from the blood to the nephron tubule. It is formed by a capillary tuft, which lies between the afferent and efferent arterioles, and by the surrounding epithelial cells of Bowman capsule. The outer layer of the glomerular capsule is called the parietal layer and consists of a single thickness of epithelial cells resting on a layer of basement membrane (Figure 26-8). The inner (visceral) layer of the capsule is composed of specialized epithelial cells called podocytes. Podocytes have foot processes (pedicels) that surround the glomerular capillary walls (Figure 26-9). Between the podocyte and the capillary endothelium is a layer of extracellular matrix called the basement membrane (see Figure 26-8).

Spaces between the endothelial cells are called fenestra, and spaces between the podocyte foot processes are called slit pores. These intercellular spaces provide the surface area for glomerular filtration and make the glomeruli considerably more permeable than other capillaries in the body (Figure 26-10). The basement membrane is an important selectivity barrier of the glomerulus, preventing plasma proteins, erythrocytes, leukocytes, and platelets from passing through. Cells are too large to pass through pores, and plasma proteins are negatively charged and repelled to some extent by the basement membrane. Slit pores have a thin diaphragm of extracellular proteins that restricts the filtration of plasma proteins that make it through the basement membrane.⁵ Nephrin, podocin, NEPH1, CD2AP, and others are important proteins in the slit pores as demonstrated by the proteinuria (protein in urine) that occurs when they are genetically mutated (Figure 26-11).⁵ Proteins and blood cells are not usually present in the urine. If the glomerulus is injured, blood cells and proteins may filter through and be found in urine. Proteinuria is an important sign of basement membrane dysfunction. Except for the lack of proteins and cells, the glomerular filtrate is very similar in composition to plasma.

The Bowman capsule drains the glomerular filtrate directly into the proximal tubule segment, where two thirds of the water and electrolytes are rapidly transported from the filtrate to the interstitium for reabsorption by peritubular capillaries6 (Figure 26-12). Nutrients, vitamins, and small proteins normally are reabsorbed completely in the early proximal tubule. The early proximal tubule is the site of most bicarbonate ion reabsorption, whereas chloride ion is reabsorbed in the late proximal tubule. The proximal tubule consists of cuboidal epithelium that is convoluted to provide a greater surface area for reabsorption. The epithelial cells in this segment have microvilli that form a brush border next to the filtrate and substantially increase the apical surface area. Proximal tubule cells have high adenosine triphosphate (ATP) requirements because most reabsorption utilizes active transport mechanisms that are dependent on Na⁺-K⁺ ion pumps in the basolateral membrane. Details of some of these transport mechanisms are discussed in subsequent sections. Water is reabsorbed passively through paracellular transport between the tubular cells and through water channels in the tubule cell membranes made of proteins called aquaporin 1. Reabsorption of solutes creates the osmotic force for passive water reabsorption.

The loop of Henle is divided into the descending and ascending limbs, which differ significantly in structure and function. The descending limb receives filtrate from the proximal convoluted tubule and delivers it to the ascending limb. The thin descending limb is permeable to water, but the thin and thick ascending part of the loop is not.6 The thick ascending segment contains powerful membrane pumps that cotransport ions (Na⁺, K⁺, 2Cl⁻) from the filtrate and deposit them in the interstitial fluid surrounding the loops of Henle and collecting ducts (Figure 26-13). About 15% of nephrons have extra-long loops of Henle that dip down into the medulla (juxtamedullary nephrons). These nephrons are vital for creating concentrated urine.

The loop formation of the loop of Henle creates a countercurrent mechanism, which allows the ascending loop of Henle to create a high interstitial gradient in the medulla of the kidney (Figure 26-14). Because the ascending loop is impermeable to water, water cannot follow the Na⁺, K⁺, and Cl⁻ ions that are pumped into the interstitium. The descending loop is permeable to water, and water will be drawn out by the extra ions that were pumped into the interstitium by the ascending limb. Thus, the filtrate that reaches the ascending limb will be more concentrated than the original filtrate. Delivery of a more concentrated filtrate to the ascending limb allows the Na⁺-K⁺-2Cl⁻ cotransporter to pump out a greater number of ions and reach an even higher interstitial gradient (Figure 26-15). This countercurrent mechanism creates a maximal osmolarity of about 600 mOsm/L at the tip of the loop of Henle as compared with the usual extracellular osmolarity of 280 to 300 mOsm/L at the cortex. Another 600 mOsm/L is contributed by the accumulation of urea particles in the interstitium.⁶ Urea moves passively from the filtrate into the interstitium down its concentration gradient. Urea becomes concentrated in the tubule filtrate when electrolytes and water are removed in the proximal tubule and loop of Henle. An overall interstitial osmolarity is generated that begins in the cortex at about 300 mOsm/L and increases progressively to about 1200 mOsm/L at a point deep in the medulla. This high interstitial osmolarity provides a gradient for water reabsorption from the collecting ducts as they pass through the medulla on their way to the renal pelvis. The maximal interstitial gradient attained is dependent on the length of the loops of Henle. In some animals that survive in dry climates, such as the desert mouse, very long loops of Henle create a much higher interstitial osmolarity, which allows formation of extremely concentrated urine. Fluid that is reabsorbed from collecting tubules into the medullary interstitium is picked up by the specialized capillary network called the vasa recta and returned to the venous circulation. Like other capillaries, the vasa recta passively exchange ions according to concentration gradients and passively reabsorb fluid by filtration forces. The loop structure of the vasa recta allows the capillary to passively leak accumulated solute back into the interstitium as the capillary makes its way back to the cortex from the medulla. This process minimizes the washout of the interstitial osmolality and has been called the countercurrent exchange mechanism.

The filtrate that reaches the distal tubule is normally hypoosmotic (100 mOsm/L) in comparison with plasma (280 mOsm/L) because electrolytes have been removed by the pumps in the ascending loop of Henle.7 At this point in the nephron, only 10% of the original glomerular filtrate volume remains, and further reabsorption in the distal tubule is largely under hormonal control. Aldosterone and angiotensin II (AII) stimulate the tubule cells to reabsorb sodium and water, whereas atrial natriuretic peptide (ANP) and urodilatin inhibit reabsorption.