Urinary casts
Encyclopedia
Urinary casts are cylindrical structures produced by the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 and present in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

 in certain disease states. They form in the distal convoluted tubule
Distal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...

 and collecting ducts of nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....

s, then dislodge and pass into the urine, where they can be detected by microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...

.

They form via precipitation of Tamm-Horsfall
Tamm-Horsfall protein
The Tamm-Horsfall glycoprotein also known as uromodulin is a glycoprotein that in humans is encoded by the UMOD gene. Up to 150 mg/dl of uromodulin may be excreted in the urine, making it the most abundant protein in normal urine.- Gene :...

 mucoprotein
Mucoprotein
A mucoprotein is a glycoprotein composed primarily of mucopolysaccharides. It can be found in the synovial fluid of the knees....

 which is secreted by renal tubule cells, and sometimes also by albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...

 in conditions of proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...

. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

). Tamm-Horsfall protein is particularly susceptible to precipitation in these conditions.

Casts were first described by Henry Bence Jones
Henry Bence Jones
Henry Bence Jones was an English physician and chemist.- Biography :He was born at Thorington Hall, Yoxley, Suffolk, the son of Lieutenant Colonel William Jones, an officer in the 5th Dragoon Guards, and Matilda Bence...

 (1813-1873).
As reflected in their cylindrical form, casts are generated in the small distal convoluted tubule
Distal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...

s and collecting ducts of the kidney, and generally maintain their shape and composition as they pass through the urinary system. Although the most common forms are benign, others indicate disease. All rely on the inclusion or adhesion of various elements on a mucoprotein base—the hyaline cast. "Cast" itself merely describes the shape, so an adjective
Adjective
In grammar, an adjective is a 'describing' word; the main syntactic role of which is to qualify a noun or noun phrase, giving more information about the object signified....

 is added to describe the composition of the cast. Various casts found in urine sediment may be classified as follows.

Hyaline casts

The most common type of cast, hyaline casts are solidified Tamm-Horsfall mucoprotein
Tamm-Horsfall protein
The Tamm-Horsfall glycoprotein also known as uromodulin is a glycoprotein that in humans is encoded by the UMOD gene. Up to 150 mg/dl of uromodulin may be excreted in the urine, making it the most abundant protein in normal urine.- Gene :...

 secreted from the tubular epithelial cells of individual nephrons. 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. Hyaline casts are cylindrical and clear, with a low refractive index, so that they can easily be missed on cursory review under brightfield microscopy, or in an aged sample where dissolution has occurred. On the other hand, phase contrast microscopy leads to easier identification. Given the ubiquitous presence of Tamm-Horsfall protein, other cast types are formed via the inclusion or adhesion of other elements to the hyaline base.

Granular casts

The second-most common type of cast, granular casts can result either from the breakdown of cellular casts or the inclusion of aggregates of plasma proteins (e.g., 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

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. It is seen in chronic renal failure.

In nephritic syndrome
Nephritic syndrome
Nephritic syndrome is a collection of signs associated with disorders affecting the kidneys, more specifically glomerular disorders. It is characterized by having small pores in the podocytes of the glomerulus, large enough to permit proteins and red blood cells to pass into the urine...

 many additional types of casts include broad and waxy casts if the condition is chronic (this is referred to as a telescopic urine with the presence of many casts).

Fatty casts

Formed by the breakdown of lipid-rich epithelial cells, these are hyaline casts with fat globule inclusions, yellowish-tan in color. 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

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
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...

, myoglobin in rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...

, and bilirubin in liver disease. Drug pigments, such as phenazopyridine, may also cause cast discoloration.

Crystal casts

Though crystallized urinary solutes, such as oxalates, urates, or sulfonamides, may become enmeshed within a ketanaline cast during its formation, the clinical significance of this occurrence is not felt to be great.

Red blood cell casts

The presence of red blood cells within the cast is always pathological, and is strongly indicative of glomerular damage, which can occur in glomerulonephritis from various causes or vasculitis, including Wegener's granulomatosis
Wegener's granulomatosis
Wegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...

, systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

, post-streptococcal glomerulonephritis or Goodpasture’s syndrome. They can also be associated with renal infarction
Infarction
In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...

 and subacute bacterial endocarditis. They are a yellowish-brown color and are generally cylindrical with sometimes ragged edges; their fragility makes inspection of a fresh sample necessary. They are usually associated with nephritic syndrome
Nephritic syndrome
Nephritic syndrome is a collection of signs associated with disorders affecting the kidneys, more specifically glomerular disorders. It is characterized by having small pores in the podocytes of the glomerulus, large enough to permit proteins and red blood cells to pass into the urine...

s or urinary tract injury.

White blood cell casts

Indicative of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 or infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

, the presence of white blood cells within or upon casts strongly suggests pyelonephritis
Pyelonephritis
Pyelonephritis is an ascending urinary tract infection that has reached the pyelum or pelvis of the kidney. It is a form of nephritis that is also referred to as pyelitis...

, a direct infection of the kidney. They may also be seen in inflammatory states, such as acute allergic interstitial nephritis
Interstitial nephritis
Interstitial nephritis is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules...

, nephrotic syndrome, or post-streptococcal acute glomerulonephritis. White cells sometimes can be difficult to discern from epithelial cells and may require special staining. Differentiation from simple clumps of white cells can be made by the presence of hyaline matrix.

Bacterial casts

Given their appearance in pyelonephritis, these should be seen in association with loose bacteria, white blood cells, and white blood cell casts. Their discovery is likely rare, due to the infection-fighting efficiency of neutrophils, and the possibility of misidentification as a fine granular cast.

Epithelial cell casts

This cast is formed by inclusion or adhesion of desquamated epithelial cells of the tubule lining. Cells can adhere in random order or in sheets and are distinguished by large, round nuclei and a lower amount of cytoplasm. These can be seen in acute tubular necrosis
Acute tubular necrosis
Acute tubular necrosis or is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water . Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely...

 and toxic ingestion, such as from mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...

, diethylene glycol
Diethylene glycol
Diethylene glycol is an organic compound with the formula 2O. It is a colorless, practically odorless, poisonous, and hygroscopic liquid with a sweetish taste. It is miscible in water, alcohol, ether, acetone, and ethylene glycol. DEG is a widely used solvent...

, or salicylate. In each case, clumps or sheets of cells may slough off simultaneously, depending of the focality of injury. Cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

 and viral hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

are organisms that can cause epithelial cell death as well.

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