KIDNEY

General Organization

Superficial Anatomic Features

In all species, the two kidneys are retroperitoneal and positioned either flat against the lumbar muscles or suspended from the dorsal abdomen. The right kidney is usually slightly more cranial than the left. The renal artery and vein, lymphatics, nerves, and the ureter pass through a single indentation or hilus. The surface of the kidney is covered by a fibrous capsule, which is composed primarily of collagen fibers, but which also may contain smooth muscle and blood vessels.

The kidneys of domesticated animals have various shapes (Fig. 11-1). In dogs, cats, sheep, and goats, the external surface of the kidney is smooth and bean-shaped. In pigs, the kidneys are smooth, elongated, and flattened. In horses, the kidneys are smooth, but only the left kidney is bean-shaped whereas the right kidney is heart-shaped. In large ruminants, the overall shape is oval, but multiple lobes are visible on the surface.

The simplest form of the mammalian kidney is the unipapillary kidney, with a single renal pyramid that includes the base next to the cortex and an apex or papilla. The unipapillary kidney is common in laboratory animals and represents the basic unit of more complex kidneys, which are formed of multiple lobes that are fused to a variable extent. Cats, dogs, horses, sheep, and goats have unilobar kidneys with papillae that are fused to form a sin gle renal crest that empties into the renal pelvis (Fig. 11-1). Pigs, large ruminants, and humans have a multilobar (multipyramidal) kidney with numerous medullary pyramids and papillae. The papillae discharge into extensions of the renal pelvis or ureter called calices (minor or major) or into the pelvis directly.

FIGURE 11-1 Schematic drawing of the gross structure and lobation pattern in three different kidneys. A. Unilobar kidney typical of carnivores. B. Multilobar kidney typical of large ruminants. On the surface of the kidney, each lobe is distinctly outlined by deep grooves. Note that this kidney lacks a renal pelvis. C. Multilobar kidney of the pig. Note the smooth surface. In the bovine kidney, the lobes are clearly demarcated (bracket in B.), while in the porcine kidney, cortical portions of the lobes fuse (bracket in C.). In the carnivore kidney (as well as in equine and small ruminant kidneys), lobes fuse extensively (bracket in A.) to give the appearance of a single lobe (“unilobar”). (Redrawn from Dellmann H-D, Brown EM. Textbook of Veterinary Histology. Philadelphia: Lea & Febiger, 1987.)

Cortex and Medulla

A longitudinal or transverse section through the kidney reveals the parenchyma, which is divided into the outer, dark red cortex and the inner, lighter-colored medulla (Figs. 11-1 and 11-2). The structures within the renal cortex are arranged in medullary rays and the cortical labyrinth (Figs. 11-2 and 11-3). These terms arose because, unlike the medulla, which is composed entirely of straight tubule segments, the renal cortex contains both straight tubule segments and convoluted tubule segments. In a transverse section, the medulla appears striated throughout and the straight segments in the cortex, which are aligned more or less in parallel bundles, appear to radiate from the medulla out toward the fibrous capsule, thus “medullary rays.” The medullary rays contain the cortical collecting ducts, cortical thick ascending limbs of the loop of Henle, and the proximal straight tubule. Sections of the cortical labyrinth contain irregular profiles of convoluted tubules including proximal convoluted tubule, distal convoluted tubule and connecting segment, as well as renal corpuscles, the distal thick ascending limb (which diverges from the medullary ray to contact the juxtaglomerular apparatus of the glomerulus), and initial collecting tubule.

The outer medulla is located deep to the cortex; the arcuate blood vessels mark the border between the cortex and the outer medulla (Fig. 11-4). The outer medulla is subdivided into outer and inner stripes. The outer stripe is the outermost region of the outer medulla and contains proximal straight tubules (S₃ segments), thick ascending limbs, and collecting ducts. The inner stripe is the inner portion of the outer medulla. The inner stripe contains no proximal tubules; the transition from proximal straight tubules to thin descending limbs of Henle’s loop marks the border between the outer and inner stripes. Thus, the inner stripe contains the collecting ducts, thick ascending limbs, and thin descending limbs of Henle’s loop.

The inner medulla is located deep to the outer medulla. Transitions between the thin limbs and thick ascending limbs of Henle’s loop mark the border between the inner and outer medulla. Thus, the inner medulla contains no thick ascending limb segments, only collecting ducts and descending and ascending thin limbs of Henle’s loop in addition to capillaries and lymphatics. Macroscopically, the inner medulla can be subdivided into the base and the papilla or renal crest. The base is adjacent to the outer medulla. The papilla, or renal crest, is the terminal portion of the inner medulla, which extends into the renal pelvis or calices.

FIGURE 11-2 Kidney (cat). Cortex (C) and small part of medulla (M). The cortex is composed of the cortical labyrinth (CL) and medullary rays (MR). The renal corpuscles and convoluted tubules are in the cortical labyrinth. The medullary rays contain long straight tubules, including proximal straight tubules, thick ascending limbs of Henle’s loop, and cortical collecting ducts. Note the capsular veins (V) at the surface of the kidney. Hematoxylin and eosin (×30).

Parts of the Renal Corpuscle and the Renal Tubule

The following lists the components of the renal corpuscle and the segments of the renal tubule in sequence from where the filtrate is formed to where it is released as urine:

FIGURE 11-3 Kidney (horse). Section cut parallel to the surface of the kidney, deep in the cortex. The medullary rays (MR) are cut in cross section and contain roughly circular profiles of straight tubules. The cortical labyrinth (CL) surrounds the medullary rays. Note the interlobular artery (IlA) and vein (IlV) in the cortical labyrinth. Hematoxylin and eosin (×55).

FIGURE 11-4 Schematic drawing of the relationships between various segments of the nephron and collecting duct and regions of the kidney. Long-looped (left) and short-looped (right) nephrons are illustrated. Cortical collecting duct (CCD); connecting segment (CNT); cortical thick ascending limb (CTAL); distal convoluted tubule (DCT); initial inner medullary collecting duct (IMCD_i); terminal inner medullary collecting duct (IMCD_t); medullary thick ascending limb (MTAL); outer medullary collecting duct (OMCD); proximal convoluted tubule (PCT); proximal straight tubule (PST); thin limb of the loop of Henle (TL). Glomeruli, PCT, DCT, terminal segments of the CTAL, and CNT are located in the cortical labyrinth; PST, CTAL, and CCD are located in the medullary rays in the cortex. (From Madsen KM, Verlander JW. Renal structure in relation to function. In: Wilcox CS, Tisher CC, eds. Handbook of Nephrology and Hypertension. 5th Ed. Philadelphia: Lippincott Williams and Wilkins, 2004.)

Nephron

Traditionally, the nephron is considered the structural and functional unit of the kidney and includes the glomerulus and all renal tubule segments through the connecting segment. The number of nephrons varies among species. Dogs have approximately 400,000 per kidney, whereas cats have approximately 200,000 per kidney. In carnivores and pigs, species in which the young are fairly immature when born, the formation of nephrons may continue for several weeks after birth. After renal maturity, no new nephrons can be formed.

Nephrons can be classified either by the location of their glomeruli in the cortex as superficial (near the capsule), midcortical, or juxtamedullary (near the medulla), or by the length of their loop of Henle as short-looped or long-looped (Fig. 11-4). Short-looped nephrons generally have superficial or midcortical glomeruli and tubules that extend only into the outer medulla before reflecting back into the cortex. In pigs, the loops turn in the medullary ray in the cortex. Long-looped nephrons have juxtamedullary glomeruli and tubules that extend into the inner medulla before reflecting back into the cortex. Most species have both short- and long-looped nephrons. However, cats, dogs, and many species native to arid climates have only long-looped nephrons, which conserve water more efficiently than short-looped nephrons. Conversely, beavers, which live in fresh water, have only short-looped nephrons.

Renal Corpuscle

General Structure

The renal corpuscle is composed of the glomerular capillary tuft, the mesangium, and the glomerular capsule, also known as Bowman’s capsule (Figs. 11-5 and 11-6). Although the term glomerulus formerly referred to only the glomerular capillary tuft and mesangium, the term is now widely used to refbegins at the urinary pole of theer to the entire renal corpuscle. The renal corpuscle is spherical and varies in size among species. Larger animals tend to have larger corpuscles. For example, horse corpuscles average 220 µm in diameter, whereas cat corpuscles average 120 µm in diameter. Blood vessels enter and exit the glomerulus at the vascular pole. The urinary pole is opposite the vascular pole where the glomerular capsule opens into the proximal convoluted tubule.

Glomerular Capillaries

The glomerular capillary tuft, or glomerular rete, is a network of branching and anastomosing capillaries. These capillaries are lined by an extremely thin layer of fenestrated endothelium; the diameter of the endothelial fenestrations or pores ranges from 50 to 150 nm (Fig. 11-7). Blood enters via the afferent arteriole and leaves via the efferent arteriole at the vascular pole (Fig. 11-6).

FIGURE 11-5 Renal corpuscle (horse). The glomerulus, composed of numerous capillary loops (C) and mesangial cells (not easily distinguished here), is surrounded by the glomerular capsule made up of a visceral layer of podocytes (P) and a parietal layer of squamous cells (arrow). The glomerular filtrate collects in the urinary space (US) of the glomerular capsule. The macula densa (MD) of the juxtaglomerular apparatus is located in the thick ascending limb of the vascular pole of the renal corpuscle. JB-4 plastic. Hematoxylin and eosin and phloxine (×335).

The glomerular basement membrane (GBM) separates the endothelial cells on its inner surface from the visceral epithelial cells, or podocytes, which cover its outer surface (Fig. 11-7). The GBM is composed of three layers: the lamina rara interna, the layer adjacent to the endothelium; the lamina rara externa, the layer adjacent to the podocytes; and the lamina densa, the layer between the laminae rara. The terms lamina rara and lamina densa refer to the electron density of the layers when viewed with a transmission electron microscope, lamina rara being electron-lucent and thus pale, and lamina densa being electron-dense, and thus dark on electron micrographs. The GBM is 100- to 250-nm thick in dogs and is composed largely of type IV collagen, heparan sulfate proteoglycans, and the glycoproteins laminin, fibronectin, and entactin. The GBM is stained by the periodic acid-Schiff (PAS) reaction, which facilitates the microscopic evaluation of the glomeruli in renal biopsies.

FIGURE 11-6 Schematic drawing of the renal corpuscle and juxtaglomerular apparatus. The afferent arteriole (AA) supplies the glomerulus, and the efferent arteriole (EA) carries blood away. The endothelial cells (E) lining the arterioles are not porous, whereas those of the glomerulus have endothelial pores (EP). The mesangial cells (MC) of the glomerulus are on the same side of the glomerular basement membrane (GBM) as the endothelial cells. The glomerular capsule surrounds the glomerulus; the complex podocytes (P) cover the capillaries and form the visceral layer that reflects at the vascular pole and is continuous with the parietal layer of simple, squamous epithelial cells (PGC). The podocyte foot processes contact the GBM; the spaces between the foot processes are the filtration slits (FS). The urinary space (US) is continuous with the lumen of the proximal convoluted tubule (PCT). The juxtaglomerular apparatus includes the macula densa (MD) within the thick ascending limb (TAL), the extraglomerular mesangial cells (EMC), the juxtaglomerular cells (JGC), and the afferent and efferent arterioles which contain smooth muscle (SM) in the tunica media. Nerve endings (NE) are found near the juxtaglomerular cells. (Redrawn from Koushanpour E, Kriz W. Renal Physiology. Principles, Structure and Function. New York: Springer-Verlag, 1986.)

Mesangium

The mesangium forms the core of the glomerulus and is composed of specialized contractile cells embedded in an acellular matrix (Fig. 11-6). Mesangial cells have elongated, irregular cell processes, contain bundles of microfilaments made up of contractile proteins, and are joined to adjacent mesangial cells by gap junctions. The functions of mesangial cells include phagocytosis, production of the mesangial matrix, maintenance of the coherence of the capillary loops, and regulation of glomerular blood flow through regulation of capillary resistance. The mesangial matrix is characterized by a dense network of microfibrils surrounded by an amorphous material that is similar to the GBM.

FIGURE 11-7 Transmission electron micrograph of glomerular basement membrane (rat). The blood within the glomerular capillary (C) is selectively filtered as it passes through the endothelial pores (EP), the three layers of the glomerular basement membrane (lamina rara interna [LRI], lamina densa [LD], and lamina rara externa [LRE]) and the filtration slits (FS) between the podocytic foot processes to enter the urinary space (US). Note the filtration diaphragms (arrows), which bridge adjacent foot processes (×67,000).

Glomerular Capsule

The glomerular capsule (Bowman’s capsule) surrounds the glomerulus (Figs. 11-5 and 11-6). The relationship of the glomerular capillary tuft to the glomerular capsule has been compared to a fist pushed into a partially inflated balloon. The fist represents the glomerular capillary tuft, the part of the balloon directly covering the fist represents the visceral epithelium, and the outer layer of the balloon not touching the fist represents the parietal epithelium. The space between the visceral and parietal layers is the urinary space (Bowman’s space) (Figs. 11-6 and 11-7).

The visceral epithelial cells, or podocytes, cover the outer surface of the glomerular capillaries (Figs. 11-8, 11-9, and 11-10). The visceral epithelial cell body contains the nucleus and is the origin of several large, primary processes from which smaller secondary and tertiary processes emanate. The smallest of these are called foot processes or pedicels. The secondary and tertiary foot processes of one cell interdigitate with those of adjacent cells. The narrow spaces (25 to 60 nm) between the foot processes are called filtration slits, which are bridged by the slit diaphragm (Fig. 11-7). The parietal epithelium, a layer of simple squamous epithelium that lines the capsule, makes an abrupt transition at the urinary pole to the cuboidal proximal tubule epithelium (Fig. 11-11).

FIGURE 11-8 Scanning electron micrograph of glomerulus (rat) as seen from the urinary space. The parietal layer of the glomerular capsule has been removed, revealing the visceral layer of podocytes embracing the glomerular capillaries. The large, smooth-surfaced cell bodies of the podocytes extend primary processes that branch into secondary and tertiary processes (pedicels). (×1300).

An additional epithelial cell in Bowman’s capsule is the peripolar cell. Peripolar cells are located at the vascular pole of the glomerulus at the junction between the parietal and visceral epithelia facing the urinary space and are largest and most numerous in sheep and goats. Peripolar cells contain dark-staining, membrane-bounded granules that contain albumin, transthyretin, immunoglobulins, neuron-specific enolase, and kallikrein, but not renin. The cells also contain adseverin, a protein involved in exocytosis in secretory cells. Thus, it is believed that the peripolar cell is a secretory cell, but its specific function is unknown.

FIGURE 11-9 Scanning electron micrograph of podocyte (rat). The cell body (C) of one podocyte is in the center of the field. Numerous processes of varying size extend from the cell body, wrap around the glomerular capillaries, and interdigitate with secondary and tertiary processes of other podocytes (×4100).

FIGURE 11-10 Schematic drawing of the components of the filtration barrier of the kidney. The capillaries consist of the glomerular basement membrane (GBM) lined by the endothelium (E), which contains numerous endothelial pores (EP) or fenestrations. Podocytes (P) cover the outer side of the GBM; the primary processes (PP) branch into secondary and tertiary processes, forming small foot processes (FP). Components of the plasma pass through the endothelial pores, the GBM, and the filtration slits (FS) and form the glomerular filtrate in the urinary space (US).

Renal Tubule

Proximal Tubule

The proximal tubule begins at the urinary pole of the renal corpuscle (Figs. 11-11 and 11-12 and Table 11-1). The proximal tubule is by far the longest cortical tubule segment and thus proximal tubule profiles dominate histologic sections of the cortex. The first portion of the proximal tubule is called the proximal convoluted tubule (PCT), because it twists and turns in the cortical labyrinth until it enters the medullary ray, where it becomes the proximal straight tubule (PST). The PST runs through the medullary ray and extends into the outer stripe of the outer medulla. Proximal tubule segments are also classified as segments S₁, S₂, and S₃, based on differences in the length or abundance of features that are common to all proximal tubule cells.

FIGURE 11-11 Scanning electron micrograph of the parietal layer of the glomerular capsule (rat). All the components of the renal corpuscle have been removed except the parietal layer. Each squamous cell of the parietal layer is distinctly outlined and projects a single, centrally located cilium. The opening into the proximal convoluted tubule (P) is surrounded by cells with a brush border, demonstrating the abrupt transition from the parietal epithelium to proximal tubule epithelium (×1200).

FIGURE 11-12 Cortical labyrinth (perfused rat kidney). The cortical labyrinth contains the renal corpuscles, proximal convoluted tubules (P), distal convoluted tubules (D), connecting segments, initial collecting tubules, and the terminal segment of the thick ascending limb. Two of the three renal corpuscles visible here show the continuity with proximal convoluted tubules. The periodic acid-Schiff (PAS) stain used on this section enhances the staining of the glomerular basement membrane, the basement membrane around the tubules, and the cell coat associated with the brush border of the proximal convoluted tubules. PAS (×335).

TABLE 11-1 Names of the Renal Tubule Segments With Corresponding Nomina Histologica Terminology

In general, the apical surface of the proximal tubule is covered by a brush border formed by extensive projections of the apical plasma membrane called microvilli (Figs. 11-13 and 11-14). The lateral borders of the epithelial cells are characterized by elaborate interdigitation of lateral cell processes. In addition, the basal surface of the cells has a remarkably folded membrane with processes from adjacent cells located between the folds. The arrangement of the epithelial cells is like a group of buttressed tree stumps packed closely together with their roots growing beneath one another. The apical brush border and the basolateral plasma membrane infoldings significantly increase the surface area of the cell and thus permit the high rates of transepithelial transport that occur in this segment.

Numerous long mitochondria are interposed among the lateral plasma membrane folds, creating vertical striations that are visible by light microscopy. The close association of the mitochondria with the plasma membrane provides a ready source of energy for adenosine triphosphate (ATP)-dependent transport proteins located in the basolateral plasma membrane.

Near the apical surface, the lateral sides of the cells are joined together by tight junctions (zonulae occludens), zonulae adherens, and desmosomes (maculae adherens). Occasional gap junctions also link the cells. The tight junctions form continuous bands around the cells, but in the proximal tubule the tight junctions are relatively permeable to solutes and water, compared to the tight junctions of distal tubule and collecting duct segments. The single nucleus is spherical and situated in the middle to basal part of the cell. Proximal tubule cells contain an extensive endocytotic apparatus including numerous apical vesicles, endosomes, and lysosomes. Peroxisomes, organelles that contain oxidative enzymes for metabolism of toxic substances, are abundant in the PST. In cats, the PCT cells contain numerous lipid droplets (Fig. 11-15). In dogs, PST cells contain similar lipid droplets and thus the medullary rays appear lighter than the surrounding parenchyma (Fig. 11-16).

Unfortunately, the distinctive structural features of proximal tubules are not evident in many histologic sections because interruption of blood flow to the kidney causes collapse of the tubules, swelling of the epithelial cells, obliteration of the tubule lumens, and disintegration of the brush border. Many of the structural features that exist in the live animal can only be preserved with careful perfusion fixation techniques.

The PST extends into the outer medulla and typically makes an abrupt transition to the simple squamous epithelium of the thin descending limb (Fig. 11-17) at the border between the inner and outer stripes of the outer medulla. In dogs, the change occurs at the corticomedullary junction; therefore, the dog kidney lacks an outer stripe.

FIGURE 11-13 Proximal convoluted tubule (dog). The brush border composed of microvilli covers the apical surface of the cells. White vacuoles near the lumen and dark, round granules deeper in the cytoplasm are endocytotic vacuoles and lysosomes, respectively. The elongated dark structures oriented perpendicular to the basement membrane are mitochondria. Epon-Araldite. Azure II, methylene blue (×1320).

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