Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

U N I T 7

often within a matter of months. The disorder involves focal and segmental proliferation of glomerular cells and recruitment of monocytes and macrophages with the for- mation of crescent structures that obliterate the Bowman space. 5 Rapidly proliferative glomerulonephritis may be caused by a number of immunologic disorders, some sys- temic and others restricted to the kidney. Among the dis- eases associated with this form of glomerulonephritis are immune complex disorders such as SLE, and an aggres- sive form of glomerulonephritis called Goodpasture syndrome. Goodpasture Syndrome. An uncommon and aggres- sive form of glomerulonephritis, Goodpasture syndrome is caused by antibodies to the glomerular basement membrane (GBM). The anti–glomerular membrane (anti-GBM) antibodies cross-react with the pulmonary alveolar basement membrane to produce the syndrome of pulmonary hemorrhage associated with renal failure. The pathologic hallmark of anti-GBM glomerulone- phritis is diffuse linear staining of glomerular basement membranes for IgG (Fig. 25-7). The cause of the disor- der is unknown, although influenza infection and expo- sure to hydrocarbon solvent (found in paints and dyes) have been implicated in some persons, as have various drugs and cancers. There is a high prevalence of certain human leukocyte antigen subtypes (e.g., HLA-DRB1) in those affected, suggesting a genetic predisposition. 4 Treatment includes plasmapheresis to remove circu- lating anti-GBM antibodies and immunosuppressive therapy (i.e., corticosteroids and cyclophosphamide) to inhibit antibody production. Nephrotic Syndrome The nephrotic syndrome is characterized by massive pro- teinuria ( ≥ 3.5 g/day in adults) and lipiduria (e.g., free fat, oval bodies, fatty casts), along with an associated

Glomerular damage

Increased permeability to proteins Proteinuria ( 3.5 g/24 h)

Hypoproteinemia

Decreased plasma oncotic pressure

Compensatory synthesis of proteins by liver

Edema

Hyperlipidemia

FIGURE 25-8. Pathophysiology of the nephrotic syndrome.

hypoalbuminemia (<3 g/dL), generalized edema, and hyperlipidemia. 4,5,10 The nephrotic syndrome is not a specific glomerular disease, but a constellation of clini- cal findings that result from an increase in glomerular permeability and loss of plasma proteins in the urine (Fig. 25-8). The glomerular membrane acts as a size-specific bar- rier through which the glomerular filtrate must pass. An increase in permeability allows proteins to escape from the plasma into the glomerular filtrate, often leading to an excessive loss of albumin—the smallest and most abun- dant of the plasma proteins. Generalized edema, which is a hallmark of the nephrotic syndrome, results from a decrease in the plasma colloidal osmotic pressure due to the hypoalbuminemia that develops as albumin is lost from the vascular compartment (see Chapter 8). There is also salt and water retention, which aggravates the edema. Initially, the edema presents in dependent parts of the body such as the lower extremities, but becomes more generalized as the disease progresses (Fig. 25-9). Dyspnea due to pulmonary edema, pleural effusions, and diaphragmatic compromise due to ascites can develop in persons with nephrotic syndrome. The hyperlipidemia that occurs in persons with ne- phrosis is characterized by elevated levels of triglyc- erides and low-density lipoproteins (LDLs). Levels of high-density lipoproteins (HDLs) usually are normal. It is thought that these abnormalities are related, at least in part, to increased synthesis of lipoproteins in the liver sec- ondary to a compensatory increase in albumin produc- tion. 13 Because of the elevated LDL levels, persons with nephrotic syndrome are at increased risk for development of atherosclerosis.

FIGURE 25-7. Anti–glomerular basement membrane glomerulonephritis. Linear immunofluorescence for IgG is seen along the glomerular basement membrane. (From Jennette JC.The kidney. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams & Wilkins; 2012:782.)