[Haematology] Microscopic Examination of Urinary Sediment - CASTS

Microscopic Examination of Urinary Sediment - CASTS, Microscopic Examination of Urinary Sediment, CASTS in urinary, Graff's Textbook of Urinalysis and Body Fluids

Urinary casts are formed in the lumen of the tubules of the kidney. They are so named because they are molded in the tubules. Casts can form as the result of the precipitation or gelation of Tamm–Horsfall mucoprotein, the clumping of cells or other material within a protein matrix, the adherence of cells or material to the matrix, or by conglutination of material within the lumen. The renal tubules secrete a mucoprotein called Tamm–Horsfall protein which is believed to form the basic matrix of all casts. Some casts may also contain serum proteins but they are usually confined to the cast granules. In waxy casts, serum proteins are present in a homogeneous distribution.

Factors that are involved in cast formation include urinary stasis (marked decrease in urine flow), increased acidity, high solute concentration, and the presence of abnormal ionic or protein constituents. Cast formation usually takes place in the distal and collecting tubules because there the urine reaches its maximum concentration and acidification. Casts will dissolve in alkaline urine and in neutral urine having a specific gravity of 1.003 or less.The presence of casts in the urine is frequently accompanied by proteinuria. However, casts can be seen in the absence of protein, making microscopic examination of urine an important tool in the diction of casts.

Casts have nearly parallel sides and rounded or blunted ends, and they vary in size and shape according to the tubules in which they were formed. They may be convoluted, straight, or curved, and they may vary in length. The width of the cast indicates the diameter of the tubule responsible for its formation. Broad casts, which can be from two to six times wider than ordinary casts, are formed either in pathologically dilated or atrophied tubules or in collecting tubules. Broad casts are frequently referred to as renal failure casts. Casts are always renal in origin, and they are important indicators of intrinsic renal disease. Disorders in which cast may be present include glomerular damage, tubular damage, renal inflammation, and renal infection. Classification of casts is made on the basis of their appearance and the cellular components that they contain. The different types of casts are hyaline, red cell, white cell, epithelial cell, granular (coarse and fine), waxy, and fatty.

Figure 5-42 Sequence of urinary cast degeneration: (1) cellular casts;

(2) coarse granular cast; (3) ﬁne granular cast; (4) waxy cast.

(Courtesy of Neil O. Hardy, Westpoint, CT.)

At times, it may be difficult to distinguish the various casts because of degeneration, or because the cast may contain a variety of structures (mixed casts). It has been proposed that as cellular casts degenerate they form granular casts that in turn degenerate, forming waxy casts (Fig. 5-42).

Casts are cylindrical in shape and do not have dark edges. Occasionally, waxy casts may appear to have a thin dark edge but only because the shiny surface of the cast comes to an abrupt ending. Usually, this thin dark edge will disappear when the fine adjustment is turned slightly. Any structure, therefore, that has dark edges is most likely a piece of fiber. In addition, any structure with parallel sides that is flat in the middle with thick edges is probably also a fiber. Remember, renal tubules are round, so casts will be more or less circular and will be thicker in the middle.

Casts are reported according to type and the number that is present per low-power field (100). Ranges reported are usually none seen, 0–2, 2–5, 5–10, 10–20/LPF.

HYALINE CASTS

Hyaline casts are the most frequently occurring casts in the urine. They are composed of gelled Tamm–Horsfall

Figure 5-43. Hyaline cast and red blood cells. Note the low refractive index of the cast (400x)

protein and may contain some inclusions which were incorporated while in the kidney. Since they are composed of only protein, they have a very low refractive index and must be viewed under low light. They are colorless, homogeneous, and transparent, and usually have rounded ends (Fig. 5-43).

Hyaline casts can be seen in even the mildest kind of renal disease and are not associated with any one disease in particular.30 A few hyaline casts may be found in the normal urine, and increased amounts are frequently present following physical exercise37,38 and physiologic dehydration.

RED BLOOD CELL CASTS

Red blood cell casts mean renal hematuria and they are always pathologic. They are usually diagnostic of glomerular disease being found in acute glomerulonephritis, lupus nephritis, Goodpasture syndrome, subacute bacterial endocarditis, and renal trauma. Red cell casts can also be present in renal infarction, severe pyelonephritis, right-sided congestive heart failure, renal vein thrombosis, and periarteritis nodosa.

Red blood cell casts may appear brown to almost colorless (Fig. 5-44). The cast may contain only a few RBCs in a protein matrix, or there may be many cells packed close together with no visible matrix. If the red cells are still intact and the outlines are still detectable, then the cast is termed a red cell cast. If the cast has degenerated to a reddish-brown granular cast, then the cast is a hemoglobin or blood cast.

WHITE BLOOD CELL CASTS

White blood cell casts are present in renal infection and in noninfectious inflammation. They can, therefore, be seen in acute pyelonephritis, interstitial nephritis, and lupus nephritis. They may also be present in glomerular disease. The majority of white cells that appear in casts are polymorphonuclear neutrophils. The WBCs in the cast may be few in number, or there may be many cells tightly packed together (Fig. 5-45). If the cells are still intact, the nuclei may be clearly visible, but as they disappear, the cast becomes granular in appearance.

GRANULAR CASTS

Granular casts may be the result of the degeneration of cellular casts or they may represent the direct aggregation of serum proteins into a matrix of Tamm–Horsfall mucoprotein. Initially, the granules are large and coarse, but when urine stasis is prolonged, these granules break down to fine granules. Granular casts almost always indicate significant renal disease; however, granular casts may be present in the urine for a short time following strenuous exercise.

Determining whether a cast is coarsely or finely granular is of no clinical significance, although the distinction is not hard to make. Finely granular casts contain fine granules which may appear gray or pale yellow in color (Fig. 5-46). Coarsely granular casts contain larger granules that are darker in color and these casts often appear black because of the density of the granules(Fig. 5-47).

Figure 5-44. Red cell cast and RBCs (400x)

EPITHELIAL CELL CASTS

Epithelial cell casts form as the result of stasis and the desquamation of renal tubular epithelial cells. These casts are only rarely seen in the urine because of the infrequent occurrence of renal diseases which primarily affect the tubules (necrosi). Epithelial cell casts may be present in urine after exposure to nephrotoxic agents or viruses (e.g., cytomegalovirus, hepatitis virus), which cause damage that accompanies glomerular injury, and in the rejection of a kidney allograft.

The epithelial cells may either be arranged in parallel rows in the cast or may be arranged haphazardly and vary in size, shape, and stage of degeneration (Fig. 5-48). The cells in the former type of arrangement are believed to come from the same segment of the tubule, whereas the irregular

arrangement seems to indicate that the cells came from different portions of the tubule.

WAXY CASTS

Waxy casts have a very high refractive index, are yellow, gray, or colorless, and have a smooth homogeneous appearance (Figs. 5-49 and 5-50). They frequently occur as short broad casts with blunt or broken ends, and they oftenhave cracked or serrated edges. It has been postulated that waxy casts result from the degeneration of granular casts. Waxy casts are found in patients with severe chronic renal failure, malignant hypertension, renal amyloidosis, and diabetic nephropathy. They may also be found in acute renal disease, tubular inflammation and degeneration, and during renal allograft rejection.

FATTY CASTS

Fatty casts are casts which have incorporated either free fat droplets or oval fat bodies (refer to the section on Oval Fat Bodies). These casts may contain only a few fat droplets, or the cast may be composed almost entirely of fat droplets of various sizes. Figure 5-51 shows a typical fatty cast with large fat droplets in half of the cast and smaller yellow–brown droplets in the other half. If the fat is cholesterol, the droplets will be anisotropic, and under polarized light will demonstrate a characteristic “Maltese-cross” formation. Isotropic droplets, which consist of triglycerides, will not polarize but will stain with Sudan III or Oil Red O.

Fatty casts are seen when there is fatty degeneration of the tubular epithelium, as in degenerative tubular disease. They are frequently seen in the nephrotic syndrome and may occur in diabetic glomerulosclerosis, lipoid nephrosis, chronic glomerulonephritis, Kimmelstiel–Wilson syndrome, lupus, and toxic renal poisoning.