Gross Anatomy

The kidneys are paired organs that lie on the posterior wall of the abdomen behind the peritoneum on either side of the vertebral column. In an adult human, each kidney weighs between 115 and 170 g and is approximately 11 cm long, 6 cm wide, and 3 cm thick.

The gross anatomic features of the human kidney are illustrated in Figure 32-1. The medial side of each kidney contains an indentation through which pass the renal artery and vein, nerves, and pelvis. If a kidney were cut in half, two regions would be evident: an outer region called the cortex and an inner region called the medulla. The cortex and medulla are composed of nephrons (the functional units of the kidney), blood vessels, lymphatics, and nerves. The medulla in the human kidney is divided into conical masses called renal pyramids. The base of each pyramid originates at the corticomedullary border, and the apex terminates in a papilla, which lies within a minor calyx. Minor calyces collect urine from each papilla. The numerous minor calyces expand into two or three open-ended pouches, the major calyces. The major calyces in turn feed into the pelvis. The pelvis represents the upper, expanded region of the ureter, which carries urine from the pelvis to the urinary bladder. The walls of the calyces, pelvis, and ureters contain smooth muscle that contracts to propel the urine toward the urinary bladder.

Figure 32-1 Structure of a human kidney, cut open to show the internal structures.

(Modified from Marsh DJ: Renal Physiology. New York, Raven, 1983.)

Blood flow to the two kidneys is equivalent to about 25% (1.25 L/min) of the cardiac output in resting individuals. However, the kidneys constitute less than 0.5% of total body weight. As illustrated in Figure 32-2 (left), the renal artery branches progressively to form the interlobar artery, the arcuate artery, the interlobular artery, and the afferent arteriole, which leads into the glomerular capillaries (i.e., glomerulus). The glomerular capillaries come together to form the efferent arteriole, which leads into a second capillary network, the peritubular capillaries, which supply blood to the nephron. The vessels of the venous system run parallel to the arterial vessels and progressively form the interlobular vein, arcuate vein, interlobar vein, and renal vein, which courses beside the ureter.

Figure 32-2 Left, Organization of the vascular system of the human kidney. 1, interlobar arteries; 1a, interlobar vein; 2, arcuate arteries; 2a, arcuate veins; 3, interlobular arteries; 3a, interlobular veins; 4, stellate vein; 5, afferent arterioles; 6, efferent arterioles; 7a, 7b, glomerular capillary networks; 8, descending vasa recta; 9, ascending vasa recta. Right, Organization of the human nephron. A superficial nephron is illustrated on the left and a juxtamedullary (JM) nephron is illustrated on the right. The loop of Henle includes the straight portion of the proximal tubule (PT), descending thin limb (DTL), ascending thin limb (ATL), and thick ascending limb (TAL). B, Bowman’s capsule; CCD, cortical collecting duct; DT, distal tubule; IMCD, inner medullary collecting duct; MD, macula densa; OMCD, outer medullary collecting duct; P, pelvis.

(Modified from Kriz W, Bankir LA: Am J Physiol 254:F1, 1988; and Koushanpour E, Kriz W: Renal Physiology: Principles, Structure, and Function, 2nd ed. New York, Springer-Verlag, 1986.)

Ultrastructure of the Nephron

The functional unit of the kidneys is the nephron. Each human kidney contains approximately 1.2 million nephrons, which are hollow tubes composed of a single cell layer. The nephron consists of a renal corpuscle, proximal tubule, loop of Henle, distal tubule, and collecting duct system^* (Fig. 32-3; also see Fig. 32-4). The renal corpuscle consists of glomerular capillaries and Bowman’s capsule. The proximal tubule initially forms several coils, followed by a straight piece that descends toward the medulla. The next segment is the loop of Henle, which is composed of the straight part of the proximal tubule, the descending thin limb (which ends in a hairpin turn), the ascending thin limb (only in nephrons with long loops of Henle), and the thick ascending limb. Near the end of the thick ascending limb, the nephron passes between the afferent and efferent arterioles of the same nephron. This short segment of the thick ascending limb is called the macula densa. The distal tubule begins a short distance beyond the macula densa and extends to the point in the cortex where two or more nephrons join to form a cortical collecting duct. The cortical collecting duct enters the medulla and becomes the outer medullary collecting duct and then the inner medullary collecting duct.

Figure 32-3 Diagram of a nephron, including the cellular ultrastructure.

Figure 32-4 Scanning electron micrograph illustrating primary cilia (C) in the apical plasma membrane of principal cells in the cortical collecting duct. Note that intercalated cells do not have cilia. Primary cilia are approximately 2 to 30 μm long and 0.5 μm in diameter. CD, collecting duct principal cells with short microvilli (arrowhead); the straight ridges (open arrow) represent the cell borders between principal cells; IC1 and IC2, intercalated cells with numerous long microvilli in the apical membrane.

(From Kriz W, Kaissling B: Structural organization of the mammalian kidney. In Seldin DW, Giebisch G [eds]: The Kidney: Physiology and Pathophysiology, 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2000.)

Each nephron segment is made up of cells that are uniquely suited to perform specific transport functions (Fig. 32-3). Proximal tubule cells have an extensively amplified apical membrane (the urine side of the cell) called the brush border, which is present only in the proximal tubule. The basolateral membrane (the blood side of the cell) is highly invaginated. These invaginations contain many mitochondria. In contrast, the descending and ascending thin limbs of Henle’s loop have poorly developed apical and basolateral surfaces and few mitochondria. The cells of the thick ascending limb and the distal tubule have abundant mitochondria and extensive infoldings of the basolateral membrane.

The collecting duct is composed of two cell types: principal cells and intercalated cells. Principal cells have a moderately invaginated basolateral membrane and contain few mitochondria. Principal cells play an important role in reabsorption of NaCl (see Chapter 33 and 34) and secretion of K⁺ (see Chapter 35). Intercalated cells, which play an important role in regulating acid-base balance, have a high density of mitochondria. One population of intercalated cells secretes H⁺ (i.e., reabsorbs HCO₃⁻), and a second population secretes HCO₃⁻ (see Chapter 36). The final segment of the nephron, the inner medullary collecting duct, is composed of inner medullary collecting duct cells. Cells of the inner medullary collecting duct have poorly developed apical and basolateral surfaces and few mitochondria.

All cells in the nephron, except intercalated cells, have in their apical plasma membrane a single nonmotile primary cilium that protrudes into the tubule fluid (Fig. 32-4). Primary cilia are mechanosensors (i.e., they sense changes in the rate of flow of tubule fluid) and chemosensors (i.e., they sense or respond to compounds in the surrounding fluid), and they initiate Ca⁺⁺-dependent signaling pathways, including those that control kidney cell function, proliferation, differentiation, and apoptosis (i.e., programmed cell death).

Nephrons may be subdivided into superficial and juxtamedullary types (Fig. 32-2). The renal corpuscle of each superficial nephron is located in the outer region of the cortex. Its loop of Henle is short, and its efferent arteriole branches into peritubular capillaries that surround the nephron segments of its own and adjacent nephrons. This capillary network conveys oxygen and important nutrients to the nephron segments in the cortex, delivers substances to the nephron for secretion (i.e., movement of a substance from blood into tubular fluid), and serves as a pathway for return of reabsorbed water and solutes to the circulatory system. A few species, including humans, also possess very short superficial nephrons whose loops of Henle never enter the medulla.

The renal corpuscle of each juxtamedullary nephron is located in the region of the cortex adjacent to the medulla (Fig. 32-2, right). When compared with superficial nephrons, juxtamedullary nephrons differ anatomically in two important ways: the loop of Henle is longer and extends deeper into the medulla, and the efferent arteriole forms not only a network of peritubular capillaries but also a series of vascular loops called the vasa recta.

As shown in Figure 32-2, the vasa recta descend into the medulla, where they form capillary networks that surround the collecting ducts and ascending limbs of the loop of Henle. The blood returns to the cortex in the ascending vasa recta. Although less than 0.7% of the renal blood flow (RBF) enters the vasa recta, these vessels subserve important functions in the renal medulla, including (1) conveying oxygen and important nutrients to nephron segments, (2) delivering substances to the nephron for secretion, (3) serving as a pathway for the return of reabsorbed water and solutes to the circulatory system, and (4) concentrating and diluting the urine (urine concentration and dilution are discussed in more detail in Chapter 34).

Ultrastructure of the Renal Corpuscle

The first step in urine formation begins with passive movement of a plasma ultrafiltrate from the glomerular capillaries (i.e., glomerulus) into Bowman’s space. The term ultrafiltration refers to the passive movement of an essentially protein-free fluid from the glomerular capillaries into Bowman’s space. To appreciate the process of ultrafiltration one must understand the anatomy of the renal corpuscle. The glomerulus consists of a network of capillaries supplied by the afferent arteriole and drained by the efferent arteriole (Figs. 32-5 and 32-6). During embryological development, the glomerular capillaries press into the closed end of the proximal tubule to form the Bowman capsule of a renal corpuscle. The capillaries are covered by epithelial cells called podocytes that form the visceral layer of Bowman’s capsule (Figs. 32-7 through 32-9). The visceral cells face outward at the vascular pole (i.e., where the afferent and efferent arterioles enter and exit Bowman’s capsule) to form the parietal layer of Bowman’s capsule. The space between the visceral layer and the parietal layer is Bowman’s space, which at the urinary pole (i.e., where the proximal tubule joins Bowman’s capsule) of the glomerulus becomes the lumen of the proximal tubule.

Figure 32-5 Anatomy of the renal corpuscle and juxtaglomerular apparatus. The juxtaglomerular apparatus is composed of the macula densa (MD) of the thick ascending limb, extraglomerular mesangial cells (EGM), and renin- and angiotensin II–producing granular cells (G) of the afferent arterioles (AA). BM, basement membrane; BS, Bowman’s space; EA, efferent arteriole; EN, endothelial cell; FP, foot processes of the podocyte; M, mesangial cells between capillaries; P, podocyte cell body (visceral cell layer); PE, parietal epithelium; PT, proximal tubule cell.

(Modified from Kriz W, Kaissling B. In Seldin DW, Giebisch G [eds]: The Kidney: Physiology and Pathophysiology, 2nd ed. New York, Raven, 1992.)

Figure 32-6 Scanning electron micrograph of the interlobular artery, afferent arteriole (af), efferent arteriole (ef), and glomerulus. The white bars on the afferent and efferent arterioles indicate that they are about 15 to 20 μm wide.

(From Kimura K et al: Am J Physiol 259:F936, 1990.)

Figure 32-7 A, Electron micrograph of a podocyte surrounding a glomerular capillary. The cell body of the podocyte contains a large nucleus with three indentations. Cell processes of the podocyte form the interdigitating foot processes (FP). The arrows in the cytoplasm of the podocyte indicate the well-developed Golgi apparatus, and the asterisks indicate Bowman’s space. C, capillary lumen; GBM, glomerular basement membrane. B, Electron micrograph of the filtration barrier of a glomerular capillary. The filtration barrier is composed of three layers: the endothelium, basement membrane, and foot processes of the podocytes. Note the filtration slit diaphragm bridging the floor of the filtration slits (arrows). CL, capillary lumen.

(From Kriz W, Kaissling B. In Seldin DW, Giebisch G [eds]: The Kidney: Physiology and Pathophysiology, 2nd ed. New York, Raven, 1992.)

Figure 32-8 A, Scanning electron micrograph showing the outer surface of glomerular capillaries. This is the view that would be seen from Bowman’s space. Processes (P) of podocytes run from the cell body (CB) toward the capillaries, where they ultimately split into foot processes. Interdigitation of the foot processes creates the filtration slits. B, Scanning electron micrograph of the inner surface (blood side) of a glomerular capillary. This view would be seen from the lumen of the capillary. The fenestrations of the endothelial cells are seen as small 700-Å holes.

(From Kriz W, Kaissling B. In Seldin DW, Giebisch G [eds]: The Kidney: Physiology and Pathophysiology, 2nd ed. New York, Raven, 1992.).

Figure 32-9 Electron micrograph of the mesangium, the area between the glomerular capillaries containing mesangial cells. C, glomerular capillaries; cGBM, capillary glomerular basement membrane surrounded by foot processes of podocytes (PO) and endothelial cells; M, mesangial cell that gives rise to several processes, some marked by stars; mGBM, mesangial glomerular basement membrane surrounded by foot processes of podocytes and mesangial cells; US, urinary space. Note the extensive extracellular matrix surrounded by mesangial cells (triangles) (×4100).

(From Kriz W, Kaissling B. In Seldin DW, Giebisch G [eds]: The Kidney: Physiology and Pathophysiology, 2nd ed. New York, Raven, 1992.)

The endothelial cells of glomerular capillaries are covered by a basement membrane that is surrounded by podocytes (Figs. 32-5 and 32-7 to 32-9). The capillary endothelium, basement membrane, and foot processes of podocytes form the so-called filtration barrier (Figs. 32-5 and 32-7 to 32-9). The endothelium is fenestrated (i.e., contains 700-Å holes, where 1 Å = 10⁻¹⁰ m) and freely permeable to water, small solutes (such as Na⁺, urea, and glucose), and most proteins but is not permeable to red blood cells, white blood cells, or platelets. Because endothelial cells express negatively charged glycoproteins on their surface, they may retard the filtration of very large anionic proteins into Bowman’s space. In addition to their role as a barrier to filtration, the endothelial cells synthesize a number of vasoactive substances (e.g., nitric oxide [NO], a vasodilator, and endothelin-1 [ET-1], a vasoconstrictor) that are important in controlling renal plasma flow (RPF).

The basement membrane, which is a porous matrix of negatively charged proteins, including type IV collagen, laminin, the proteoglycans agrin and perlecan, and fibronectin, is an important filtration barrier to plasma proteins. The basement membrane is thought to function primarily as a charge-selective filter in which the ability of proteins to cross the filter is based on charge.^*

The podocytes, which are endocytic, have long finger-like processes that completely encircle the outer surface of the capillaries (Fig. 32-8). The processes of the podocytes interdigitate to cover the basement membrane and are separated by apparent gaps called filtration slits. Each filtration slit is bridged by a thin diaphragm that contains pores with a dimension of 40 × 140 Å. The filtration slit diaphragm, which appears as a continuous structure when viewed by electron microscopy (Fig. 32-7, B), is composed of several proteins, including nephrin (NPHS1), NEPH-1, podocin (NPHS2), α-actinin 4 (ACTN4), and CD2-AP (Figs. 32-10 and 32-11). Filtration slits, which function primarily as a size-selective filter, keep the proteins and macromolecules that cross the basement membrane from entering Bowman’s space.

Figure 32-10 Anatomy of podocyte foot processes. This figure illustrates the proteins that make up the slit diaphragm between two adjacent foot processes. Nephrin and NEPH1 are membrane-spanning proteins that have large extracellular domains that interact. Podocin, also a membrane-spanning protein, organizes nephrin and NEPH1 in specific microdomains in the plasma membrane, which is important for signaling events that determine the structural integrity of podocyte foot processes. Many of the proteins that compose the slit diaphragm interact with adapter proteins inside the cell, including CD2-AP. The adapter proteins bind to the filamentous actin (F-actin) cytoskeleton, which in turn binds either directly or indirectly to proteins such as α3β1 and MAGI-1 that interact with proteins expressed by the glomerular basement membrane (GBM). α-act-4, α-actinin 4; α₃β₁, α₃β₁ integrin; α-DG, α-dystroglycan; CD2-AP, an adapter protein that links nephrin and podocin to intracellular proteins; FAT, a protocadherin that organizes actin polymerization; MAGI-1, a membrane-associated guanylate kinase protein; NHERF-2, Na⁺-H⁺ exchanger regulatory factor 2; P, paxillin; P-Cad, P-cadherin; Synpo, synaptopodin; T, talin; V, vinculin; Z, zona occludens.

(Adapted from Mundel P, Shankland SJ: J Am Soc Nephrol 13:3005, 2002.)