Chapter 7 Nonprotein Nitrogen Compounds (2)

Nonprotein Nitrogen Compounds

• Chapter 7

Introduction

• Functions of the Kidney:

  • Removal of waste, toxic, and surplus products from the body.

  • Maintenance of homeostasis of body water levels.

  • Regulation of acid-base levels and electrolytes.

  • Hormonal regulation.

• Renal Function Tests include:

  • Blood Urea Nitrogen (BUN).

  • Creatinine levels.

  • Electrolytes (sodium Na, potassium K, chloride Cl).

  • Nonprotein nitrogen (NPN).

• Nonprotein Nitrogen:

  • Products of protein and nucleic acid catabolism.

  • Contain nitrogen but are not part of a protein.

  • Removed from the body by the kidneys.

Blood Urea Nitrogen (Urea Nitrogen)

• Major nitrogen-containing metabolic product from protein catabolism.

• Factors affecting BUN levels:

  • Urea concentration.

  • Glomerular filtration rate (GFR).

  • Body hydration.

• Clinical significance:

  • Uremia: Increased urea in the blood.

  • Azotemia: Increased levels of BUN and other NPNs—classified as prerenal, renal, or postrenal.

  • Decreased BUN levels may indicate different clinical issues.

• BUN methodologies:

  • Enzymatic urease method.

  • Diacetyl reaction.

Creatinine (CR)

• Waste product from the metabolism of creatine and phosphocreatine:

  • Reaction: Phosphocreatine + ADP → Creatine + ATP.

  • Reaction: Creatine → Creatinine + H2O.

• Factors affecting creatinine levels:

  • Relative muscle mass.

  • Creatine turnover rate.

  • Renal function.

• Clinical significance:

  • Serves as an index of renal function (GFR).

• Methodologies for measuring creatinine include:

  • Jaffe reaction (creatinine and picric acid).

  • Enzymatic creatininase (creatinine amidohydrolase with creatine kinase).

Uric Acid

• Major product of nucleoprotein catabolism produced in the liver from xanthine:

  • Reaction: Xanthine → Uric acid.

• Clinical significance:

  • Primary hyperuricemia: Excess uric acid in blood.

  • Secondary hyperuricemia.

  • Hypouricemia: Low uric acid levels.

• Methodologies:

  • Phosphotungstic acid method.

  • Uricase and Xanthine oxidase method.

Creatinine Clearance (CrCl)

• Most popular and practical method for estimating GFR:

  • Freely filtered by glomeruli, not significantly reabsorbed by tubules.

  • Released into plasma at a constant rate.

• Calculation includes:

  • Serum creatinine level.

  • Urine creatinine level.

  • Urine volume corrected for body surface area (BSA).

• Clinical significance:

  • Decreased CrCl indicates decreased GFR and potential renal damage.

  • Increased CrCl generally not clinically significant.

  • Formulas:

    • U = urine concentration (mg/dL).

    • P = plasma concentration (mg/dL).

    • V = urine flow (mL/min).

Estimated GFR (eGFR)

• Estimation of GFR using serum creatinine levels.

• Utilizes the Modification of Diet in Renal Disease (MDRD) equation based on:

  • Serum/plasma creatinine level.

  • Age.

  • Gender.

  • Race.

• eGFR Calculator is available through the National Kidney Foundation.

Other Methods for GFR

• Protein:Creatinine Ratio:

  • Predicts the presence of significant proteinuria.

• Inulin Clearance:

  • Inulin injected, serum, and urine levels measured over 3 hours.

  • Fewer practical methodologies; requires extensive procedures including water loading and bladder catheterization.

• Cystatin C:

  • Freely filtered by glomeruli, catabolized in the proximal convoluted tubule (PCT).

  • Produced at constant rate; levels affected by various factors.

Ammonia

• Produced during the catabolism of amino acids:

  • Converted to urea in the liver and excreted as ammonium ion by the kidneys.

• Clinical concerns:

  • Extremely toxic to human cells.

  • Elevated levels in severe liver disease, Reye’s syndrome, and inherited urea cycle enzyme deficiencies.

• Methodologies for measuring ammonia:

  • Ion-selective electrode.

  • Spectrophotometric methods.

  • Enzymatic methods.

  • Special specimen handling requirements are necessary.