Chapter 20 - The Kidney

Charles E. Alpers MD

Normal

What is a human but an ingenious machine designed to turn, with "infinite artfulness, the red wine of Shiraz into urine"? So said the storyteller in Isak Dinesen's Seven Gothic Tales.[1]

More accurately but less poetically, human kidneys serve to convert more than 1700 liters of blood per day into about 1 liter of a highly specialized concentrated fluid called urine. In so

doing, the kidney excretes the waste products of metabolism, precisely regulates the body's concentration of water and salt, maintains the appropriate acid balance of plasma, and serves as

an endocrine organ, secreting such hormones as erythropoietin, renin, and prostaglandins. The physiologic mechanisms that the kidney has evolved to carry out these functions require a

high degree of structural complexity.

Each human adult kidney weighs about 150 gm. As the ureter enters the kidney at the hilum, it dilates into a funnel-shaped cavity, the pelvis, from which derive two or three main branches,

the major calyces; each of these subdivides again into three or four minor calyces. There are about 12 minor calyces in the human kidney. On the cut surface, the kidney is made up of a

cortex and a medulla, the former 1.2 to 1.5 cm in thickness. The medulla consists of renal pyramids, the apices of which are called papillae, each related to a calyx. Cortical tissue extends

into spaces between adjacent pyramids as the renal columns of Bertin. From the standpoint of its diseases, the kidney can be divided into four components: blood vessels, glomeruli,

tubules, and interstitium.

Blood Vessels.

The kidney is richly supplied by blood vessels, and although both kidneys make up only 0.5% of the total body weight, they receive about 25% of the cardiac output. The cortex is by far

the most richly vascularized part of the kidney, receiving 90% of the total renal blood supply. The main renal artery divides into anterior and posterior sections at the hilum. From these,

interlobar arteries emerge, course between lobes, and give rise to the arcuate arteries, which arch between cortex and medulla, in turn giving rise to the interlobular arteries. From the

interlobular arteries, afferent arterioles enter the glomerular tuft, where they progressively subdivide into 20 to 40 capillary loops arranged in several units or lobules architecturally

centered by a supporting mesangial stalk. Capillary loops merge to exit from the glomerulus as efferent arterioles. In general, efferent arterioles from superficial nephrons form a rich

vascular network that encircles cortical tubules (peritubular vascular network), and deeper juxtamedullary glomeruli give rise to the vasa recta, which descend as straight vessels to supply

the outer and inner medulla. These descending arterial vasa recta then make several loops in the inner medulla and ascend as the venous vasa recta.

The anatomy of renal vessels has several important implications. First, because the arteries are largely end-arteries, occlusion of any branch usually results in infarction of the specific area

it supplies. Glomerular disease that interferes with blood flow through the glomerular capillaries has profound effects on the tubules, within both the cortex and the medulla, because all

tubular capillary beds are derived from the efferent arterioles. The peculiarities of the blood supply to the renal medulla render them especially vulnerable to ischemia; the medulla does

not have its own arterial blood supply but is dependent on the blood emanating from the glomerular efferent arterioles. The blood in the capillary loops in the medulla has a remarkably

low level of oxygenation. Thus, minor interference with the blood supply of the medulla may result in medullary necrosis from ischemia.

Glomeruli.

The glomerulus consists of an anastomosing network of capillaries lined by fenestrated endothelium invested by two layers of epithelium ( Fig. 20-1 ). The visceral epithelium is

incorporated into and becomes an intrinsic part of the capillary wall, separated from endothelial cells by a basement membrane. The parietal epithelium, situated on Bowman's capsule,

lines the urinary space, the cavity in which plasma filtrate first collects.

The glomerular capillary wall is the filtering membrane and consists of the following structures[2] ( Fig. 20-2 ):

• A thin layer of fenestrated endothelial cells, each fenestrum being about 70 to 100 nm in diameter.

• A glomerular basement membrane (GBM) with a thick electron-dense central layer, the lamina densa, and thinner electron-lucent peripheral layers, the lamina rara interna and

lamina rara externa. The GBM consists of collagen (mostly type IV), laminin, polyanionic proteoglycans (mostly heparan sulfate), fibronectin, entactin, and several other

glycoproteins. Type IV collagen forms a network

suprastructure to which other glycoproteins attach. The building block (monomer) of this network is a triple-helical molecule made up of three a-chains, composed of one or more of six

types of a-chains (a1to a6or COL4A1 to COL4A6), the most common consisting of a1, a2, a1( Fig. 20-3). [3]Each molecule consists of a 7S domain at the amino terminus, a triple-helical

domain in the middle, and a globular noncollagenous domain (NC1) at the carboxyl terminus. The NC1 domain is important for helix formation and for assembly of collagen monomers

into the basement membrane suprastructure. Glycoproteins (laminin, entactin) and acidic proteoglycans (heparan sulfate, perlecan) attach to the collagenous suprastructure[3][4][5]( Fig. 20-

4). These biochemical determinants are critical to understanding glomerular diseases.For example, as we shall see, the antigens in the NC1 domain are the targets of antibodies in anti-

GBM nephritis; genetic defects in the a-chains underlie some forms of hereditary nephritis; and the acidic porous nature of the GBM determines its permeability characteristics.

• The visceral epithelial cells (podocytes), are structurally complex cells that possess interdigitating processes embedded in and adherent to the lamina rara externa of the basement

membrane. Adjacent foot processes (pedicels) are separated by 20- to 30-nm-wide filtration slits, which are bridged by a thin diaphragm (see Fig. 20-2 ).

• The entire glomerular tuft is supported by mesangial cells lying between the capillaries. Basement membrane-like mesangial matrix forms a meshwork through which the

mesangial cells are centered ( Fig. 20-1 ). These cells, of mesenchymal origin, are contractile, phagocytic, and capable of proliferation, of laying down both matrix and collagen,

and of secreting a number of biologically active mediators. Biologically, they are most akin to vascular smooth muscle cells and pericytes. They are, as we shall see, important

players in many forms of human glomerulonephritis.

Figure 20-1 A, Low-power electron micrograph of renal glomerulus. CL, capillary lumen; MES, mesangium; END, endothelium; EP, visceral epithelial cells with foot processes.

(Courtesy of Dr. Vicki Kelley, Brigham and Women's Hospital, Boston, MA.) B, Schematic representation of a glomerular lobe.

Figure 20-2Glomerular filter consisting, from bottom to top, of fenestrated endothelium, basement membrane, and foot processes of epithelial cells. Note the filtration slits (arrows) and

diaphragm. Note also that the basement membrane consists of a central lamina densa, sandwiched between two looser layers, the lamina rara interna and lamina rara externa. (Courtesy of

Dr. Helmut Rennke, Brigham and Women's Hospital, Boston, MA.)

Figure 20-3Schematic illustration of type IV collagen supramolecular network assembly. A, Six genetically distinct a-chains (a1 to a6) assemble into three distinct protomers. The

protomers are characterized by a long central collagen triple helix, the 7S domain at the N terminus, and a globular NC1 trimer at the C terminus. B, NC1 domains provide specificity for

chain association, alignment, registration, and propagation from the C- to N-terminal direction. This sequence of events, shown for the a1, a2 protomer, is true for other protomers also.

(Courtesy of Dr. Billy Hudson, Vanderbilt University, Nashville, TN, reprinted with permission.)

Figure 20-4 A proposed model of the GBM molecular architecture in which type IV collagen monomers (gray) form a stable network through their NC1 domains (dimeric interactions,

gray spheres) and 7S domains (tetrameric interactions) and intertwine along the triple-helical domains. Laminin monomers (red) separately form a reversible meshwork. Entactin (green)

connects laminin to the collagen network and binds to perlecan (blue), an anionic heparan sulfate proteoglycan. This anionic suprastructure determines the charged porous nature of the

GBM. (Courtesy of Dr. Peter Yurchenco, Robert W. Johnson Medical School, Piscataway, NJ.)

Figure 20-5Schematic diagram of the proteins of the glomerular slit diaphragm. CD2AP, CD2-associated protein.

TABLE 20-1-- Principal Systemic Manifestations of Chronic Renal Failure and Uremia

Date: 2016-04-22; view: 687