Renal Anatomy and Basic Concepts and Methods in Renal Pathology

Arthur H. Cohen

Normal Anatomy

Each kidney weighs approximately 150 g in adults, with ranges of 125 to 175 g for men and 115 to 155 g for women; both together represent 0.4% of the total body weight. Each kidney is supplied by a single renal artery originating from the abdominal aorta; the main renal artery branches to form anterior and posterior divisions at the hilus and divides further, its branches penetrating the renal substance proper as interlobar arteries, which course between lobes. Interlobar arteries extend to the corticome-dullary junction and give rise to arcuate arteries, which arch between cortex and medulla and course roughly perpendicular to interlobar arteries. Interlobular arteries, branches of arcuate arteries, run perpendicular to the arcuate arteries and extend through the cortex toward the capsule (Fig. 1.1). Afferent arterioles branch from the interlobular arteries and give rise to glomerular capillaries (Fig. 1.2). A glomerulus represents a spherical bag of capillary loops arranged in several lobules (Fig. 1.3); the capillaries merge to exit the glomerulus as efferent arterioles, which, in most nephrons, branch to form another vascular bed, peritubular or interstitial capillaries, which surround tubules. Efferent arterioles from juxtamedul-lary glomeruli extend into the medulla as vasa recta, which supply the outer and inner medulla. The vasa recta and peritubular capillaries collect, forming into interlobular veins; the veins follow the arteries in distribution, size, and course, and leave the kidneys as renal veins, which empty into the inferior vena cava.

The kidneys have three major components: the cortex, the medulla, and the collecting system. On the cut surface, the cortex is the pale outer region, approximately 1.5 cm in thickness, which has a granular appearance because of the presence of glomeruli and convoluted tubules. The medulla, a series of pyramidal structures with apical papillae, number normally eight to 18, and have a striped or striated appearance because of the parallel arrangement of the tubular structures. The bases of the pyramids are at the corticomedullary junction and the apices extend into the collecting

Nephronophthisis Kidney Pathology
Figure 1.1. Low magnification of cortex with portions of two glomeruli, tubules, and interstitium and interlobular artery with arteriolar branch [periodic acid-Schiff (PAS) stain].
Figure 1.2. A: Low magnification of cortex. An arcuate artery (AA), interlobular artery (IA), and afferent arteriole (aa) are in continuity (Jones silver stain). B: Interlobular artery (IA) with afferent arteriole (aa) extending into glomerulus (Masson trichrome stain).
Artery Masson Staining
Figure 1.3. Normal glomerulus with surrounding normal tubules and interstitium (Jones silver stain).

system. Cortical parenchyma extends into spaces between adjacent pyramids; this portion of the cortex is known as the columns of Bertin. A medullary pyramid with surrounding cortical parenchyma, which includes both columns of Bertin as well as the subcapsular cortex, constitutes a renal lobe. The collecting system consists of the pelvis, which represents the expanded upper portion of the ureter, and is more or less funnel shaped. Each pelvis has two or three major branches known as the major calyces. Each calyx divides further into three or four smaller branches known as minor calyces, each usually receiving one medullary papilla.

Each kidney contains approximately 1 million nephrons, each composed of a glomerulus and attached tubules. Glomeruli are spherical collections of interconnected capillaries within a space (Bowman's space) lined by flattened parietal epithelial cells (Fig. 1.3). Bowman's space is continuous with the tubules, with the orifice of the proximal tubule generally at the pole opposite the glomerular hilus, where the afferent and efferent arteri-oles enter and leave, respectively. The outer aspects of the glomerular capillaries are covered by a layer of visceral epithelial cells or podocytes. Each visceral epithelial cell has a large body containing the nucleus and cytoplasmic extensions, which divide, forming small finger-like processes that interdigitate with similar structures from adjacent cells and cover the capillaries. These interdigitating processes, known as pedicles, are also called foot processes because of their appearance on transmission electron microscopy. The space between adjacent foot processes is known as the filtration slit; adjacent foot processes are joined together by a thin membrane known as the slit-pore diaphragm. Epithelial cells cover the glo-merular capillary basement membrane, a three-layer structure with a central thick layer slightly electron dense (lamina densa) and thinner electron lucent layers beneath epithelial and endothelial cells (lamina rara externa and lamina rara interna, respectively) (Fig. 1.4). The glomerular basement membrane is composed predominately of type IV collagen with small amount type V collagen, laminin, and proteoglycans, predominantly heparan sulfate. In addition, entactin and fibronectin are present. The glomerular basement membrane in adults measures approximately 340 to 360 nanometers (nm) in thickness and is significantly thicker in men than in women. The endothelial cells are thin and have multiple fenestrae, each measuring approximately 80 nm in diameter. The capillary tufts are supported by the mesangium, which represents the intraglomerular continuation of the arteriolar walls. The mesangium has two components. The extracellular one, mesangial matrix, has many structural, compositional, and, therefore, tinctorial properties similar to basement membrane. The cells of the mesangium are known as mesangial cells, of which there are two types: modified smooth muscle cells, representing greater than 95% of the cellular population, and bone marrow-derived cells, representing the remainder. Mesangial cells have numerous functions including contraction, production of extracellular matrix, secretion of inflammatory and other active mediators, phagocytosis, and migration from the central zone where they are normally situated (Fig. 1.5).

The proteoglycans of the glomerular basement membrane are negatively charged; similarly, the surface of both epithelial and endothelial cells are anionically charged because of sialoglycoproteins in the cellular coats. Both of these negatively charged structures are responsible for the charge-selective barrier to filtration of capillary contents. The basement membrane, which, along with the fenestrated endothelial cell, allows for ready filtration of water and small substances, is known as the size-selective

Figure 1.4. Portion of glomerular capillary wall by electron microscopy. Individual foot processes of visceral epithelial cells (arrows) cover the basement membrane and endothelial cell cytoplasm (arrowhead) lines the lumen.
Figure 1.5. Portion of glomerulus indicating different cell types: capillary endothelial cell (EN), visceral epithelial cell (VEC), and mesangial cell (MC) (electron microscopy).

barrier. The visceral epithelial cell in the adult is responsible for the production and maintenance of basement membrane.

The remaining portion of the nephron is divided into proximal tubules, which are often convoluted, the loop of Henle, with both descending and ascending limbs, and the distal tubule. The proximal tubular cells have well-developed closely packed microvillous luminal surfaces known as the brush border. The cells are larger than those of the distal tubules, which have relatively few surface microvilli. Each tubule is surrounded completely by a basement membrane. Adjacent tubular basement membranes are in almost direct contact with one another and separated by a small amount of connective tissue known as the interstitium, which contain peri-tubular capillaries (Fig. 1.6). At the vascular pole of the glomerulus and

Figure 1.6. Normal cortical tubules, interstitium, and peritubular capillaries; most of the tubules are proximal, with well-defined brush borders (PAS stain).

the site of entrance of the afferent arteriole, the cells of the arteriolar wall are modified into secretory cells known as juxtaglomerular cells; these produce and secrete renin, contained in granules. The macula densa, a portion of the distal tubule at the glomerular hilus, is characterized by smaller and more crowded distal tubular cells, which are in contact with the juxtaglomerular cells. Surrounding the macula densa and afferent arteriole are lacis cells, which are mesenchymal cells similar to mesangial cells.

Examination of Renal Tissue

Because of the types of diseases and the renal components that are abnormal, the preparation of tissue specimens for examination is somewhat complex considering the required methods of study. These include sophisticated light microscopy, immunofluorescence, and electron microscopy. For light microscopy, the elucidation of lesions of glomeruli mandates that a variety of histochemical stains be used and that tissue sections be cut thinner than for other tissues. Furthermore, to take best advantage of the stains, many investigators and renal pathologists have found that formalin, Zenker's solution, or many of the more commonly used fixatives result in substandard preparations. Consequently, alcoholic Bouin's solution (Duboseq-Brasil) is the fixative of choice. For the elucidation of glomerular structure and pathology, it is necessary that the extracellular matrix components (basement membrane, mesangial matrix) be preferentially stained. Table 1.1 indicates staining characteristic of normal and abnormal renal structures. In paraffin-embedded sections, the hematoxylin and eosin stain does not ordinarily allow for distinction of extracellular matrix from cytoplasm in a clear or convincing manner. Periodic acid-Schiff (PAS), periodic acid-methenamine silver (Jones), and Masson's trichrome stains all provide excellent definition of extracellular material. Each stain has its advantages and disadvantages, and as a rule, all are used in evaluating renal tissues especially biopsies. The PAS reagent stains glomerular basement membranes, mesangial matrix, and tubular basement membranes red (positive), while the Jones stain colors the same components black, providing clear contrast between positively and negatively staining structures. Masson's trichrome stain colors extracellular glomerular matrix and tubular basement membranes blue, clearly distinguished from cells and abnormal material that accumulates in pathologic circumstances. Congo red, elastic tissue, and other stains are employed when indicated. The tissue sections should be no greater than 2 to 3 |im in thickness, for the definition of glomerular pathology, especially regarding cellularity, is dependent on sections of this thickness. The ability to detect subtle pathologic abnormalities is enhanced with thinner sections. Especially for glomerular diseases, immunohisto-chemistry is necessary for evaluation renal tissues, especially for diagnosing glomerular diseases. Most laboratories utilize immunofluorescence for identifying and localizing immunoglobulins, complement, fibrin, and other

Table 1.1. Staining characteristics of selected normal and abnormal renal structures

Stain

Table 1.1. Staining characteristics of selected normal and abnormal renal structures

Stain

PAS

Jones

Masson's trichrome

Basement membrane

Red

Black

Deep blue

Mesangial matrix

Red

Black

Deep blue

Interstitial collagen

Negative

Negative

Pale blue

Cell cytoplasm (normal)

Negative (most)

Negative

Rust/orange-granular

Immune complex

Negative to

Negative

Bright red-orange

deposits

slightly positive

homogeneous

"Insudative lesions"

Negative to

Negative

Bright red-orange

slightly positive

homogeneous

Fibrin

Slightly positive

Negative

Bright red-orange

fibrillar

Other

Plasma protein

Slightly positive

Negative

Bright red-orange

precipitates

homogeneous

(intra- or

extracellular)

Amyloid

Negative

Negative

Light blue-orange

(Congo Red

(sometimes

positive)

positive)

Tubular casts

Red

Gray to black

Light blue

(Tamm-Horsfall

protein)

PAS, periodic acid-Schiff.

immune substances within renal tissues; fluorescein-labeled antibodies to the following are used: immunoglobulin G (IgG), IgA, IgM, C1q, C3, albumin, fibrin, and kappa and lambda immunoglobulin light chains. For transplant biopsies, anitbody to C4d is routinely utilized. Fluorescence positivity in glomeruli is described as granular or linear (Fig. 1.7). Regard-

Figure 1.7. Glomerular immunofluorescence indicating linear (L) and granular (G) capillary wall staining for immunoglobulin G (IgG).

Table 1.2. Immune deposits

IF

LM

EM

Granular

Trichrome stain bright red-orange

Electron dense

Linear

Not visible

Not visible

EM, electron microscopy; IF, immunofluorescence; LM, light microscopy.

EM, electron microscopy; IF, immunofluorescence; LM, light microscopy.

less of the immunopathologic mechanisms responsible for the granular deposits, there is an electron microscopic counterpart to granular deposits; by electron microscopy, extracellular masses of electron-dense material correspond to the deposits. The granular deposits can be appreciated in tissue prepared for light microscopy; this is best demonstrated and documented with the use of Masson's trichrome stain, where granular deposits appear as bright fuchsinophilic (orange, red-orange) smooth homogeneous structures. There is no regular ultrastructural or light microscopic counterpart to linear staining (Table 1.2). Electron microscopy is routinely utilized in the study of renal tissues. For glomerular and some tubulo-interstitial diseases this method is mandatory and helps localize deposits, detects extremely small deposits, and documents alterations of cellular and basement membrane structure. Immunofluorescence and electron microscopy are also often necessary and helpful in diagnosing other tubular, interstitial, and vascular lesions.

The typical appearances and tinctorial properties with routinely used stains of normal and abnormal renal structures are provided in Table 1.1.

Tamm-Horsfall Protein (THP) (Also Known as Uromodulin)

Tamm-Horsfall protein is a large glycoprotein (mucoprotein) produced only by cells of the thick ascending limb of the loop of Henle. While it has many physiologic functions, for the pathologist interested in renal tissue changes it provides important information regarding tubular structure and integrity. This glycoprotein, when precipitated in gel form in distal tubules, forms a cast of the tubular lumen, which may be passed in the urine as a hyaline cast. Thus, Tamm-Horsfall protein is the fundamental constituent of urinary casts. In tissue sections, the casts are strongly PAS positive and can easily be recognized. The structural value of this feature is that the cast material, in a variety of pathologic states, may be found in abnormal locations and therefore may provide evidence regarding pathogenesis of certain diseases and their pathophysiologic consequences. Tamm-Horsfall protein has been identified primarily in three major abnormal sites: (1) the proximal nephron, (2) the renal interstitium and occasionally intrarenal capillaries and veins, and (3) in perihilar locations. It has been documented that with intra- or extrarenal obstruction and/or reflux, THP may be found in proximal tubules and in glomerular urinary spaces, the result of retro grade flow in the nephron. Escape of THP from within the nephron into the interstitium and peritubular capillaries has been documented to occur with tubular wall disruption. There are four major mechanisms proposed for this finding: (1) increased intranephron pressure (reflux, obstruction), which can cause rupture of the tubular wall and spillage of contents locally; (2) destruction of tubular walls by infiltrating leukocytes (as in any acute interstitial nephritis); collagenases produced by infiltrating cells, especially monocytes, can dissolve basement membranes and concomitant epithelial cell damage can result in tubular wall defects; (3) in acute tubular necrosis (especially of ischemic type) both cell death and basement membrane loss have been described; interstitial and capillary and venous THP is uncommonly observed; and (4) intrinsic defects of tubular basement membranes (as in juvenile nephronophthisis), which likely result in loss of compliance of tubular walls and, in addition to cyst formation, may also lead to dissolution of part of the walls with escape of luminal contents. In all of the above, it is clear that while other tubular contents may also be in abnormal locations, it is Tamm-Horsfall protein that has the morphologic and tinctorial features that allow microscopists to identify it and use it as a marker of urine. Tamm-Horsfall protein is a weak immunogen; initially it was thought that its escape from tubules was, in large part, immunologically responsible for progression of chronic tubulo-interstitial damage in the disorders characterized by this feature. However, despite the presence of serum anti-THP antibodies in patients with reflux nephropathy, the pathogenic role of THP in immunologic renal injury is uncertain and probably not very important. Tamm-Horsfall protein has been documented to bind and inactivate inter-leukin-1 (IL-1) and tumor necrosis factor (TNF).

General Pathology of Renal Structures

Before embarking on a consideration of various renal diseases, a discussion of basic abnormalities that characterize the renal structures is presented first.

Glomeruli

Increased cellularity (hypercellularity) may result from increase in intrinsic cells (mesangial, visceral epithelial or endothelial cells) or from accumulation of leukocytes in capillary lumina, beneath endothelial cells, or in the mesangium. Although not entirely correct, glomerular lesions with increased cells in the tufts are often known as proliferative glomerulone-phritis. Accumulation of cells and fibrin within the urinary space is known as a crescent (see below).

Increase in extracellular matrix implies an increase in mesangial matrix or basement membrane material. In the former instance, this may be in a uniform and diffuse pattern in all lobules or cause a nodular appearance to the mesangium. Increased basement membrane material takes the form of thickened basement membranes, an abnormality that is best appreciated by electron microscopy.

Sclerosis refers to increased extracellular matrix and other material leading to obliteration of capillaries and solidification of all or part of the tufts. Sclerosis (glomerular scarring) may be associated with obliteration of the urinary space by collagen along with increased extracellular matrix in the capillary tufts. When the entire glomerulus is involved, this is known as complete sclerosis; an older and less precise term is glomerular hyalin-ization. Segmental glomerulosclerosis implies a completely different pathologic process and often a disease. With segmental sclerosis, only portions of the capillary tufts are involved; capillaries are obliterated by increased extracellular matrix and/or large precipitates of plasma protein known as insudates.

Crescents represent accumulation of cells and extracellular material in the urinary space. Crescents are the result of severe capillary wall damage with disruptions in continuity and spillage of fibrin from inside the damaged capillaries into the urinary spaces. This is associated with proliferation of visceral and perhaps parietal epithelial cells and accumulation of mono-cytes and other blood cells in the urinary space. The cellular composition of the crescent varies depending on the type of disease and associated damage to the basement membrane of Bowman's capsule. Crescents most commonly heal by organization (scar formation). With an admixture of cells and collagen, the crescent is considered fibrocellular, and with only collagen in the urinary space, the crescent is designated as fibrotic.

Peripheral migration and interposition of mesangium: Mesangial cells and often matrix extend from the central lobular portion of the tuft into the peripheral capillary wall, migrating between endothelial cell and basement membrane and causing capillary wall thickening with two layers of extracellular matrix. This two-layer or double-contour appearance may involve a few or all capillaries.

Alteration in visceral epithelial cell morphology: This abnormality requires the electron microscope to detect. In association with protein loss across the glomerular capillary wall, the epithelial cells change shape; the foot processes retract and swell, resulting in loss of individual foot processes and a near solid mass of cytoplasm covering the glomerular basement membrane. This loss or effacement of foot processes is also incorrectly known as fusion because it was initially thought adjacent foot processes fused with one another.

Tubules

Tubular cells may exhibit a variety of degenerative changes, or may undergo acute reversible and irreversible damage (necrosis). The degenerative lesions are often in the form of intracellular accumulations, manifestations of either local metabolic abnormalities or systemic processes. For example, lipid inclusions in proximal and, less commonly, distal tubular cells result from hyperlipidemia and lipiduria of nephrotic syndrome, and protein reabsorption droplets ("hyaline droplets") accumulate in proximal tubular cells in association with albuminuria and its reabsorption by tubular epithelium. Additional locally induced abnormalities include uniform fine cytoplasmic vacuolization consequent to hypertonic solution infusion (e.g., mannitol, sucrose). Tubular cells may be sites of "storage" of hemosiderin in patients with chronic intravascular hemolysis, high iron load, or glomerular hematuria. Few metabolic storage diseases affect tubular epithelium; among others are cystinosis with crystals and glycogen storage diseases and diabetes mellitus with abundant intracellular glycogen. Vacuoles, especially large and irregular, may be associated with hypokalemia.

On the other hand, reversible and irreversible changes are features of acute tubular necrosis. These include loss of brush border staining for proximal cells, diffuse flattening of cells with resulting dilatation of lumina, loss of individual lining cells, and sloughing of cells into lumina. Manifestations of repair or regeneration include cytoplasmic basophilia and mitotic figures.

The morphologic features of atrophy of tubules include not only diminution in caliber, but more importantly irregular thickening and wrinkling of basement membranes. Adjacent tubules are invariably separated from one another in this circumstance. The intervening interstitium is almost always fibrotic, with or without accompanying inflammation. Other structural forms of tubular atrophy include uniform flattening of cells, hyaline casts in dilated lumina, and close approximation of tubules, resulting in a thyroid-like appearance to the parenchyma.

Interstitium

There are limited structural manifestations of interstitial injury. Commonly observed are edema, inflammation, and fibrosis. Both cortical edema and fibrosis are associated with separation of normally closely apposed tubules. With edema only, the tubular basement membranes are of normal thickness and contour. In contrast, with fibrosis the tubules are invariably atrophied with thickened and irregularly contoured basement membranes. The distinction between an acute and a chronic interstitial process is made based on the presence of edema (acute) or fibrosis (chronic) regardless of the character of any infiltrating leukocytes. With interstitial inflammation, especially when acute, the leukocytes, which gain access to the interstitium from the peritubular capillaries, usually extend into the walls of tubules. During this process, there may be damage to and destruction of tubular basement membranes as well as degeneration of epithelial cells. This often results in spillage of tubular contents into the interstitium.

The type(s) of cells in an interstitial inflammatory infiltrate depend(s) on the nature of the inflammatory process. For example, polymorphonuclear leukocytes, as expected, are present in early phases of many bacterial infections; however, they do not remain and are usually replaced by lymphocytes, plasma cells, and monocytes approximately 7 to 10 days following the onset of infection. On the other hand, other infectious agents may elicit only a "round cell" response. Cell-mediated forms of acute inflammation, even in very early stages, are characterized by lymphocytic infiltrate, with or without plasma cells, monocytes, and granulomata.

Besides inflammatory cells, the interstitium may be infiltrated by or contain abnormal extracellular material; this includes amyloid, immuno-globulin light chains (usually along tubular basement membranes), immune complex deposits, etc. This may be in association with similar infiltrates in glomeruli, or less commonly, may be restricted to the interstitium.

Pathogenic Mechanisms in Renal Diseases

Glomerular Immunologic

Many glomerular and a small number of tubulo-interstitial and vascular disorders are immunologically mediated. These may be the result either of antibody-mediated or cell-mediated processes. In most instances in humans, the immediate cause or antigenic stimulus for the immune reaction is not known. The detection of antibody-mediated damage in renal tissue depends on the use of immunofluorescence microscopy.

Most glomerulopathies are immunologically mediated and are the result of antibody-induced injury. This can occur as a consequence of antibody combining with an intrinsic antigen in the glomerulus or antibody combining either in situ or in the circulation with an extrinsic glomerular antigen, with immune complexes localizing or depositing in glomeruli. With circulating immune complexes, the antigens may be of endogenous or exogenous origin. Endogenous antigens occur in diseases such as systemic lupus ery-thematosus and include components of nuclei such as DNA, histones, etc. Exogenous antigens are usually of microorganism origin and include bacterial products, hepatitis B and C viral antigens, malarial antigen, etc. Circulating immune complexes are trapped or lodge in glomeruli in the mesangium and subendothelial aspects of capillary walls. Less commonly, they may be found in subepithelial locations. It is the electron microscope that precisely localizes the deposits. Certain diseases are characterized by deposits in predominately one site, whereas other diseases may be charac terized by deposits in more than one location. Once immune complexes are deposited, complement is fixed and often leukocyte infiltration follows. The white blood cells accumulate in capillary lumina and infiltrate into the mesangium; in addition, intrinsic mesangial cells may divide and may also extend into peripheral capillary walls. The leukocytes, in part, may be responsible for removal of deposited immune complexes. The names of the many glomerular disorders, diagnostic criteria, and prognostic and therapeutic implications depend on the correct localization and identification of the immune complexes in the glomeruli.

The other mechanism of antibody-induced injury results from in situ immune complex formation. This can occur in two major situations. The antibody can be directed against an intrinsic component of the glomerulus such as a portion of the basement membrane or perhaps, as shown in experimental animals, a cellular component. Alternatively, antigen may arrive in the glomerulus from the circulation and be planted or trapped in a particular location. Antibody binds with the trapped antigen, forming immune complex locally.

In humans, antibody directed against the basement membrane component is known as antiglomerular basement membrane antibody. The pattern of fluorescence is of linear binding of the antibody to the basement membrane. Planted antigens and glomerular epithelial cell antigen in experimental animals, when combined with antibody in situ, result in a pattern of granular fluorescence similar to glomeruli with deposition of circulating immune complexes.

Cell-mediated immune injury in human renal disease is evident in acute interstitial disorders such as drug-induced acute interstitial nephritis and certain forms of transplant rejection. On the other hand, cell-mediated immune mechanisms in glomerular disease are postulated with sound experimental and clinical reasoning.

Complement components, especially C5b-C9, may have a large role in producing structural and functional damage, especially in glomeruli. Recent and continuing evidence has documented the important roles of cytokines especially IL-1 and TNF as well as platelet-derived growth factor (PDGF) and transforming growth factor-P (TGF-P) in the genesis and progression of glomerular disease.

Nonimmunologic

There are several important mechanisms that result in significant glomeru-lar damage in a wide variety of circumstances that merit comment here.

Damage to glomerular visceral epithelial cells, from a wide variety of influences, causes cell swelling with loss of individual foot processes. Further damage results in vacuolization, accumulation of protein in lyso-somes (protein reabsorption droplets), and detachment of cells from the basement membrane.

With significant loss of functioning nephrons, the remnant nephrons undergo hypertrophy. While initially an adaptive process, these changes are associated with the ultimate development of segmental glomerulosclerosis, diminution in glomerular filtration, and heavy proteinuria.

Tubular and Interstitial Injury

Pathogenic mechanisms in tubulo-interstitial injury include immunologic processes (antibody-mediated and cell-mediated immunity) with cytokine expression and release, and action of inflammatory mediators. Chronic changes (interstitial fibrosis and tubular atrophy) are also the result of cytokine (PDGF and TGF-P) and complement (C5) fibroblast chemoat-traction and of interaction of fibroblasts with metalloproteinases and IL-1, TNF-a, and epidermal growth factor. Fibroblasts produce collagen types I, III, IV, V; tubular cells are capable of synthesizing types I and III collagens as well as type IV (basement membrane) collagen.

Vasculature

In general, the renal arteries and arterioles respond to injuries in a manner similar to other vascular beds. However, the kidneys are frequent targets of vascular injury because of their high blood flow (approximately 25% of cardiac output); furthermore, kidney function is critically dependent on blood pressure and flow and any interference to either may have profound effects.

The major lesions affecting renal vasculature include (1) thrombosis and embolization; (2) fibrin deposition in the walls of arteries, arterioles, and glomerular capillaries; (3) inflammation and necrosis of vascular walls; and (4) arteriosclerosis. The basic pathologic features of these injuries are little different from those of vessels in other organs and tissues, and a comprehensive consideration, therefore, is not warranted except in lesions unique to renal vessels.

Perhaps the most important of these features is the vascular picture resulting from platelet activation and mural fibrin deposition. These result in different abnormalities in different-sized vessels. In small (interlobular) arteries, there is smooth muscle cell proliferation with intimal ingrowth of these cells and marked luminal narrowing. Fibrin in arteriolar walls is associated with endothelial damage and local thrombosis, often with extension of the thrombi into glomeruli. In these structures (glomeruli), endo-thelial cells are swollen, capillary walls are thickened with accumulation of fibrin beneath endothelial cells, and mesangial regions widened also because of fibrin deposition. Structural consequences include capillary microaneurysm formation. Healing results in varying degrees of mesangial sclerosis (increased matrix) and capillary wall double contours (1-6).

References

1. Cohen AH, Nast CC. The kidney. In: Damjanov I, Linder J, eds. Anderson's Pathology, 10th ed. St. Louis: Mosby, 1996:2071-2137.

2. Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. Heptinstall's Pathology of the Kidney, 5th ed. Philadelphia: Lippincott-Raven, 1998.

3. Silva FG, D'Agati VD, Nadasdy T. Renal Biopsy Interpretation. New York: Churchill Livingstone, 1996.

4. Churg J, Bernstein J, Glassock RJ, eds. Renal Disease: Classification and Atlas of Glomerular Diseases, 2nd ed. New York: Igaku-Shoin, 1995.

5. Seshan SV, D'Agati, Appel GA, Churg J. Renal Disease: Classification and Atlas of Tubulo-Interstitial and Vascular Diseases. Baltimore: Williams & Wilkins, 1999.

6. Kern WF, Silva FG, Laszik ZG, Bane BL, Nadasdy T, Pitha JV. Atlas of Renal Pathology. Philadelphia: WB Saunders, 1999.

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