Renal Pathophysiology

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RENAL PATHOPHYSIOLOGY: THE ESSENTIALS

Granular and Waxy Casts Granular and waxy casts are thought to represent successive stages in the degeneration of cellular casts as they flow through the nephron. In addition to representing cellular debris, the granules in granular casts can represent aggregated plasma proteins. Thus, granular casts can form in any proteinuric condition. Red Cells As with white cells, red cells can enter the urine (called hematuria ) at any site in the urinary tract. The bleeding may be microscopic (seen only under the microscope) or grossly visible. As little as 1 mL of blood in 1 L of urine can induce a visible color change. The most common causes of hematuria in an adult are extrarenal, in cluding kidney stones, trauma, prostatic disease, and, particularly in men over the age of 50 years, cancer of the prostate, bladder, or kidney. As a re sult, older patients usually undergo a radiologic and urologic evaluation (in cluding insertion of a cystoscope into the bladder) to exclude malignancy. Although less common, glomerular bleeding is important to identify because it can be associated with AKI and obviates the need for these diagnostic pro cedures. The following findings can be used to distinguish glomerular from extraglomerular bleeding: „ Red cell casts —Red cell casts (in which red cells are contained within casts) are virtually diagnostic of some form of glomerulonephritis or vas culitis (see Plate 8.1, Panel B). However, the absence of red cell casts does not exclude glomerular disease. „ Red cell morphology —Glomerular bleeding is typically associated with fragmentation of the red cells, leading to a dysmorphic appearance man ifested by blebs, budding, and segmental loss of the membrane. Both mechanical trauma as the red cells pass through rents in the glomerular capillary wall and osmotic trauma as the red cells pass through the differ ent nephron segments are thought to contribute to the red cell damage. In comparison, red cells that are round and uniform in size and shape (as in a normal peripheral blood smear) are more likely to have an extrarenal origin in the pelvis, ureter, bladder, prostate, or urethra (see Plate 8.2). „ Proteinuria —Protein excretion > 500 mg/day is highly suggestive of in trarenal abnormalities and can be seen with both glomerular and tubular lesions. Proteinuria in excess of 3,000 mg/day is virtually diagnostic for a glomerular lesion. „ Blood clots —Blood clots, if present in a patient with grossly visible he maturia, are almost always extrarenal in origin. Clots are rarely seen with glomerular bleeding, perhaps due to the presence of thrombolytic factors, such as urokinase and tissue-type plasminogen activators in the glomeruli and in the tubules.

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