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Urea is a highly soluble organic compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea is formed in a cyclic pathway known simply as the urea cycle. In this cycle, amino groups donated by ammonia and L-aspartate are converted to urea. Urea is essentially a waste product; it has no physiological function. It is dissolved in blood (in humans in a concentration of 2.5 - 7.5 mmol/liter) and excreted by the kidney in the urine. In addition, a small amount of urea is excreted (along with sodium chloride and water) in human sweat.
The blood urea nitrogen (BUN) test is a measure of the amount of nitrogen in the blood in the form of urea, and a measurement of renal function. Urea is a substance secreted by the liver, and removed from the blood by the kidneys. The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain between 7 and 18 to 21 mg of urea nitrogen per 100 ml (7-21 mg/dL) of blood. Individual laboratories may have different reference ranges, and this is because the procedure may vary.
The most common cause of an elevated BUN, azotemia, is poor kidney function, although a serum creatinine level is a somewhat more specific measure of renal function (see also renal function).
A greatly elevated BUN (>60 mg/dL) generally indicates a moderate-to-severe degree of renal failure. Impaired renal excretion of urea may be due to temporary conditions such as dehydration or shock, or may be due to either acute or chronic disease of the kidneys themselves.
An elevated BUN in the setting of a relatively normal creatinine may reflect a physiological response to a relative decrease of blood flow to the kidney (as seen in heart failure or dehydration) without indicating any true injury to the kidney. However, an isolated elevation of BUN may also reflect excessive formation of urea without any compromise to the kidneys.
Increased production of urea is seen in cases of moderate or heavy bleeding in the upper gastrointestinal tract (e.g. from ulcers). The nitrogenous compounds from the blood are resorbed as they pass through the rest of the GI tract and then broken down to urea by the liver. Enhanced metabolism of proteins will also increase urea production, as may be seen with high protein diets, steroid use, burns, or fevers.
A low BUN usually has little significance, but its causes include liver problems, malnutrition (insufficient dietary protein), or excessive alcohol consumption. Overhydration from intravenous fluids can result in a low BUN. Normal changes in renal bloodflow during pregnancy will also lower BUN.
Urea itself is not toxic. This was demonstrated by Johnson et al. by adding large amounts of urea to the dialysate of hemodialysis patients for several months and finding no ill effects. However, BUN is a marker for other nitrogenous waste. Thus, when renal failure leads to a buildup of urea and other nitrogenous wastes (uremia), an individual may suffer neurological disturbances such as altered cognitive function (encephalopathy), impaired taste (dysgeusia) or loss of appetite (anorexia). The individual may also suffer from nausea and vomiting, or bleeding from dysfunctional platelets. Prolonged periods of severe uremia may result in the skin taking on a grey discolouration or even forming frank urea crystals ("uremic frost") on the skin.
Because multiple variables can interfere with the interpretation of a BUN value, GFR and creatinine clearance are more accurate markers of kidney function. Age, sex, and weight will alter the "normal" range for each individual, including race. In renal failure or chronic kidney disease (CKD), BUN will only be elevated outside "normal" when more than 60% of kidney cells are no longer functioning. Hence, more accurate measures of renal function are generally preferred to assess the clearance for purposes of medication dosing.
BUN is reported as mg/dL in the United States. Elsewhere, the concentration of urea is reported as mmol/L. To convert from mg/dL of blood urea nitrogen to mmol/L of urea, divide by 2.8 (each molecule of urea having 2 nitrogens, each of molar mass 14g/mol)
Urea (in mmol/L) = BUN (in mg/dL of nitrogen) / 2.8 (from wikipedia)
Diseases / Conditions Related to Nutrition
- Bacterial meningitis
- Cirrhotic patients
Other (Monogenic) Disorders
- Argininemia OMIM: 207800
- Argininosuccinic aciduria OMIM: 207900
- Carbamoyl phosphate synthetase i deficiency, hyperammonemia due to OMIM: 237300
- Lysinuric protein intolerance OMIM: 222700
- Ornithine transcarbamylase deficiency, hyperammonemia due to OMIM: 311250