Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

U N I T 7

Two types of immune mechanisms have been impli- cated in the development of glomerular disease: (1) injury resulting from antibodies reacting with fixed glomerular antigens or antigens planted within the glomerulus and (2) injury resulting from circulating antigen–antibody complexes that become trapped in the glomerular mem- brane 4,5,12 (Fig. 25-5). Antigens responsible for develop- ment of the immune response may be of endogenous origin, such as autoantibodies to deoxyribonucleic acid (DNA) in systemic lupus erythematosus (SLE), or they may be of exogenous origin, such as streptococcal mem- brane antigens in poststreptococcal glomerulonephritis. Frequently, the source of the antigen is unknown. Glomerular diseases have traditionally been named according to tissue appearance (i.e., proliferative, mem- branous, or sclerotic) rather than according to the under- lying cause. Accordingly, the term proliferative is used to describe a hypercellular inflammatory process with pro- liferation of glomerular cells; membranous, an abnor- mal thickening of the glomerular basement membrane; and sclerotic, an increase in the amount of extracellular material in the mesangial, subendothelial, or subepi- thelial tissue of the glomerulus. 4,10 Glomerular changes can be diffuse, involving all glomeruli and all parts of the glomeruli; focal, in which only some glomeruli are affected and others are essentially normal; segmental, involving only a certain segment of each glomerulus; or mesangial, affecting only mesangial cells. Figure 25-4B illustrates the location of lesions associated with various types of glomerular disease. Dependent upon the structures involved and the extent of their involvement, glomerular disorders can manifest with hematuria (red cells in the urine), protein- uria (protein in the urine), and the presence or absence of hypertension; azotemia (elevation of blood urea nitro- gen); or renal insufficiency. The nephritic syndrome is due to glomerular disease that is usually of acute onset and is accompanied by grossly visible hematuria, mild to moderate proteinuria, and hypertension. The nephrotic syndrome , also due to glomerular disease, is character- ized by heavy proteinuria, hypoalbuminemia, and severe edema.

Epithelial cell with podocytes Endothelial cell

Mesangial matrix Mesangial cell

Basement membrane

A

Endothelial cell swelling

Mesangial deposit

White blood cell

Basement membrane

Subendothelial deposits

Subepithelial deposits

Fusion of epithelial cell podocytes

B

FIGURE 25-4. (A) Normal. (B) Localization of immune deposits (mesangial, subendothelial, subepithelial) and changes in glomerular architecture associated with injury.

The agents or events that trigger glomerular injury include infectious microorganisms, immunologic mech- anisms, drugs, and environmental agents. 4,5,10–13 Most cases of primary and many cases of secondary glomerular disease probably have an immune origin. Although many glomerular diseases are driven by immunologic events, a variety of metabolic (e.g., diabetes), hemodynamic (e.g., hypertension), and toxic (e.g., drugs, chemicals) stresses can induce glomerular injury, either alone or in concert with immunologic mechanisms.

Epithelial cell

Foot process (podocytes)

Basement membrane

FIGURE 25-5. Immune mechanisms of glomerular disease. (A) Antiglomerular membrane antibodies leave the circulation and interact with antigens that are present in the basement membrane of the glomerulus. (B) Antigen– antibody complexes circulating in the blood become trapped as they are filtered in the glomerulus.

Subendothelial deposit Circulating antigen–antibody complexes Antigen Antibody

A

B

Circulating antigen–antibody complex deposition

Antiglomerular membrane antibodies