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186. Proteinuria, haematuria, casts. Proteinuria is the abnormal presence of protein in the urine, and more than 150 mg of protein/day is considered pathological. A large quantity of protein can make your urine appear frothy. Protein in the urine indicates damage to kidneys, either from a glomerular membrane permeability defect or a defect in the renal tubules-- where filtered proteins are normally reabsorbed. A common method of testing for proteinuria is a chemically treated diptstick that changes color in the urine sample based on how much protein is present. The small amount of physiological protein appearing in the urine (less than 150 mg/day) consists of uromodulin (Tamm-Horsfall protein-secreted by tubular epithelium), albumin, and low molecular weight proteins (beta-2 microglobulin) and amino acids. One exception of physiological proteinuria is orthostatic proteinuria, most common in young adult males and is associated with prolonged upright posture throughout the day. Can yield a positive dipstick test, but with otherwise normal renal functions. Proteinuria exceeding 3500mg/day is termed nephritic syndrome. Proteinuria can be also be classified as selective or non-selective, depending on the extent of the derangement of the glomerular membrane. In non-selective proteinuria, the membrane damage is severe and even large and electrically charged proteins are excreted. (http://www.patient.co.uk/showdoc/40000542/ and Professor Necas) Haematuria is the abnormal presence of red blood cells in the urine. The source of the RBCs can be post-glomerular –from the urinary tract (caused by inflammation, stones, tumors) or the glomerular capillaries (accompanied by massive proteinuria). In theory, no RBCs should be found in the urine, and haematuria can be classified as macroscopic (red colored urine) or microscopic, where the RBCs can be detected using a chemically treated dipstick or microscopically. (http://en.wikipedia.org/wiki/Hematuria and Professor Necas) Urinary casts are formed when debris in the renal tubules aggregate into a cylindrical shape in the distal tubules, dislodge and pass into the urine. They can be identified microscopically (bright field or phase contrast) and used as prognostic indicators of kidney disorders. Some casts might require staining for differentiation (WBCs). The debris composing the casts can be acellular (hyaline, granular, waxy, fatty, pigment, crystal) or cellular elements (RBCs, WBCs, bacterial cells, epithelial cells). All casts contain uromodulin (Tamm-Horsfall mucoprotein) which is normally secreted from the tubular epithelial cells of the distal tubules, plus whatever other debris adheres or is included. The urine sample should be centrifuged, the and the pellet resuspended in a small amount of supernatant (.2-.5mL) and a drop is examined on a microscope slide. Casts can be reported quantitatively (number of casts per power field) and by content (cell type, composition). The samples should be fresh, as casts are prone to break apart if left standing too long. A few hyaline or granular casts may be considered physiological. Acellular Casts: Hyaline casts are solidified Tamm-Horsfall mucoprotein. Low urine flow, concentrated urine, or an acidic environment can contribute to the formation of hyaline casts, and as such, they may be seen in normal individuals in dehydration or vigorous exercise. Granular casts can result either from the breakdown of cellular casts, or the inclusion of aggregates of plasma proteins (albumin or immunoglobulin light chains). Depending on the size of inclusions, they can be classified as fine or coarse, though the distinction has no diagnostic significance. Their appearance is generally more cigar-shaped and of a higher refractive index than hyaline casts. While most often indicative of chronic renal disease, these casts, as with hyaline casts, can also be seen for a short time following strenuous exercise. Waxy casts are thought to represent the end product of cast evolution, waxy casts suggest the very low urine flow associated with severe, longstanding kidney disease such as renal failure. Additionally, due to urine stasis and their formation in diseased, dilated ducts, these casts are significantly larger than hyaline casts. While cylindrical, they also possess a higher refractive index and are more rigid, demonstrating sharp edges, fractures, and broken off ends. Waxy casts also fall under the umbrella of “broad” casts, a more general term to describe the wider cast product of a dilated duct. Fatty casts are formed by the breakdown of lipid rich epithelial cells, these are hyaline casts with fat globule inclusions, and are yellowish-tan in appearance. If cholesterol or cholesterol esters are present, they are associated with the “Maltese cross” sign under polarized light. They can be present in various disorders, including the high urinary protein nephrotic syndrome, diabetic or lupus nephropathy, or larger scale necrosis or epithelial cell death. Pigment casts are formed by the adhesion of metabolic breakdown products or drug pigments, these casts are so named due to their discoloration. Pigments include those produced endogenously, such as hemoglobin in hemolytic anemia, myoglobin in rhabdomyolysis, and bilirubin in liver disease. Drug pigments, such as phenazopyridine, may also cause cast discoloration. Crystal casts are crystallized urinary solutes, such as oxalates, urates, or sulfonamides, and may become enmeshed within a hyaline cast during its formation, the clinical significance of this occurrence is not felt to be great. http://en.wikipedia.org/wiki/Urinary_casts Cellular Casts: RBCs in the cast appear yellowish brown and are pathological. Causes include: systemic lupus erythematosis, post-stretpococcal glomerulonephritis, Goodpasture’s syndrome, renal infarction, and can be associated with subacute bacterial endocarditis. WBCs in the cast are indicative of infection (such as pyelonephritis) or inflammation (caused by post streptococcal glomerulonephritis, acute allergic interstitial nephritis, or nephrotic syndrome) Bacterial casts often include WBCs, maybe seen with pyelonephritis. Epithelial cell casts are the tubular lining, which can slough off due to insult or injury, including toxic ingestion (Hg), tubular necrosis, cytomegalovirus and viral hepatitis. (Acellular and cellular casts descriptions taken from: Haber, Meryl H. Urinary Sediment: A Textbook Atlas. American Society of Clinical Pathologists, Chicago. 1981.) Plagiarism sources 14.6%