1. Urea measurement

3. BIOCHEMISTRY AND PHYSIOLOGY Urea (CO[NH 2 ] 2 ) – 75% of the nonprotein nitrogen eventually Excreted. Protein catabolism – Amino acid nitrogen is converted to urea – in the liver by urea cycle Urea is excreted through – The kidneys, More than 90% Kidney disease, accumulation of urea in blood. – Gastrointestinal tract and skin

4. BIOCHEMISTRY AND PHYSIOLOGY Uremic (azotemic) state. – Increase in plasma urea

5. The urea cycle pathway CPS I, Carbamyl phosphate synthetase I; *N-acetylglutamate as positive allosteric effector; OTC, ornithine transcarbamylase; MS, argininosuccinate synthetase; AI., argininosuccinate lyase; AR, arginase; ADP, adenosine diphosphate, P I, inorganic phosphate.

6. CLINICAL SIGNIFICANCE Pre-renal conditions – High-protein diet – Increased protein catabolism – Reabsorption of blood proteins after gastrointestinal hemorrhage – Treatment with cortisol – Dehydration – Decreased perfusion of the kidneys Heart failure

7. CLINICAL SIGNIFICANCE Pre-renal conditions – Creatinine concentration may be normal. Postrenal conditions – Malignancy, nephrolithiasis, and prostatism – both plasma creatinine and urea concentrations will be increased Discriminator – Plasma urea, plasma creatinine, urea nitrogen/creatinine ratio reference interval (normal diet) – 12 and 20 mg urea/mg creatinine (49 and 81 mol urea/mol creatinine).

8. CLINICAL SIGNIFICANCE Lower ratios – Acute tubular necrosis, low protein intake, starvation, or severe liver disease (decreased urea synthesis). Urea clearance is a poor indicator of GFR – Production rate is dependent on several nonrenal factors Including diet and the activity of the urea cycle enzymes. – Variable amount of back diffusion

9. Blood urea nitrogen (BUN) – Converting urea mass units to urea nitrogen 0.467 – Converting urea nitrogen mass units to urea 2.14 – Urea nitrogen in mg/dL to urea in mmol/L 0.357.

10. ANALYTICAL METHODOLOGY Chemical Enzymatic

11. Chemical Methods Based on Fearon reaction 540 nm.

12. Enzymatic Methods Urease – Urea to ammonium ion Ammonium quantitation – Berthelot reaction – Enzymatic assay

13. assay with Glutamate dehydrogenase Decrease in absorbance at 340 nm

14. Interference Endogenous ammonium – Aged samples in some urines – Particular metabolic disorders

15. Reference Intervals Plasma Urea nitrogen in healthy adults – 6 to 20 mg/dL More than 60 years of age – 8 to 23 mg/dL Slightly lower in children and in pregnancy Slightly higher in males than in females