blood urea nitrogen

**Physiology:** Amino acid deamination produces ammonia (NH3), which the liver converts to urea via the urea cycle (carbamoyl phosphate synthetase I in mitochondria is the rate-limiting step; ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, and arginase complete the cycle). Urea is filtered freely at the glomerulus. About 40–50% is passively reabsorbed in the proximal tubule, and further reabsorption occurs in the medullary collecting duct via ADH-regulated urea transporters (UT-A1/A3). That reabsorption helps build the medullary concentration gradient. Because reabsorption rises when tubular flow is low, BUN is a less reliable GFR marker than creatinine.

**Normal range:** ~7–20 mg/dL. BUN:creatinine ratio is normally ~10–15:1.

**Elevated BUN (azotemia):** - **Prerenal (ratio >20:1):** hypovolemia, dehydration, heart failure, hepatorenal states. Low tubular flow plus ADH and RAAS activation increase urea reabsorption, while creatinine is not reabsorbed. Also FENa <1%, urine osm >500, and urine Na <20. - **Intrinsic renal (ratio ~10–15:1):** ATN (FENa >2%, muddy brown casts), AIN, and glomerulonephritis. Tubular damage impairs urea reabsorption, so the ratio falls. - **Postrenal (ratio variable, often >15):** obstruction such as BPH or stones. Early obstruction can raise the ratio, and later tubular damage lowers it. - **Non-renal causes of increased BUN with normal Cr:** upper GI bleed (digested blood protein load), high-protein diet, catabolic states (sepsis, burns, trauma), corticosteroids, tetracyclines, and TPN.

**Decreased BUN:** severe liver disease/cirrhosis (impaired urea synthesis, which also raises ammonia, as in hepatic encephalopathy), low protein intake or malnutrition, SIADH or overhydration (dilution), pregnancy, and urea cycle disorders (e.g., OTC deficiency, which has hyperammonemia, low BUN, and elevated orotic acid).

**Clinical significance:** - **Uremia** is the clinical syndrome of markedly elevated BUN. Its signs are encephalopathy, asterixis, pericarditis (friction rub), platelet dysfunction and bleeding, nausea/vomiting, and pruritus. These are indications for urgent dialysis (AEIOU: Acidosis, Electrolytes (hyperkalemia), Intoxication, Overload (volume), Uremia). - BUN is part of the BMP. It is also used in risk scores (e.g., CURB-65 for pneumonia: BUN >19 mg/dL, and the Glasgow-Blatchford score for GI bleeding). - Creatinine (from muscle creatine) is a better GFR estimate because it is less affected by diet, liver function, and volume status.

**High-yield pearls:** Prerenal azotemia has a high BUN:Cr ratio. An upper GI bleed raises BUN disproportionately. Liver failure lowers BUN. Urea reabsorption is ADH-dependent in the collecting duct.