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Acute tubular necrosis

Acute tubular necrosis

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Acute tubular necrosis or (ATN) is a medical condition involving the death of tubular cells that form the tubule
Tubule
A tubule is a very small tube or fistular structure.A system of surface-connected membranes in muscle that enables a nerve impulse to travel to the interior of the muscle fibre.In anatomy, a tubule is a minute tube lined with glandular epithelium....

 that transports 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...

 to the ureter
Ureter
In human anatomy, the ureters are muscular tubes that propel urine from the kidneys to the urinary bladder. In the adult, the ureters are usually long and ~3-4 mm in diameter....

s while reabsorbing 99% of the water (and highly concentrating the salts and metabolic byproducts). Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely. ATN presents with acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...

 (ARF) and is one of the most common causes of ARF. The presence of "muddy brown casts" of epithelial cells found in the urine during urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...

 is pathognomonic for ATN.

Classification


It may be classified as either toxic or ischemic
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

. Toxic ATN occurs when the tubular cells are exposed to a toxic substance (nephrotoxic ATN). Ischemic ATN occurs when the tubular cells do not get enough oxygen, a condition that they are highly sensitive and susceptible to, due to their very high metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

.

Diagnosis


Acute tubular necrosis is classified as a "renal" (i.e. not pre-renal or post-renal) cause of Acute renal failure. Diagnosis is made by a FeNA (fractional excretion of sodium) > 3% and presence of muddy casts in urinalysis. On histopathology, there is usually tubulorrhexis, that is, localized necrosis of the epithelial lining in renal tubules, with focal rupture or loss of basement membrane. Proximal tubule cells can shed with variable viability and not be purely "necrotic".40_75%

Toxic ATN


Toxic ATN can be caused by free hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

 or myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...

, by medication such as antibiotics such as aminoglycoside and cytoxic drugs such as cisplatin, or by intoxication (ethylene glycol
Ethylene glycol
Ethylene glycol is an organic compound widely used as an automotive antifreeze and a precursor to polymers. In its pure form, it is an odorless, colorless, syrupy, sweet-tasting liquid...

, "anti-freeze").

Histopathology
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...

: Toxic ATN is characterized by proximal tubular epithelium necrosis (no nuclei, intense eosinophilic homogeneous cytoplasm, but preserved shape) due to a toxic substance (poisons, organic solvents, drugs, heavy metals
Heavy metals
A heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...

). Necrotic cells fall into the tubule lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...

, obliterating it, and determining acute renal failure. Basement membrane is intact, so the tubular epithelium regeneration is possible. Glomeruli are not affected.

Ischemic ATN


Ischemic ATN can be caused when the kidneys are not sufficiently perfused for a long period of time (i.e. renal artery stenosis
Renal artery stenosis
Renal artery stenosis is the narrowing of the renal artery, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney...

) or during shock. Hypoperfusion can also be caused by embolism
Embolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...

of the renal arteries.
Ischemic ATN specifically causes skip lesions through the tubules.

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