NPN

• except from protein, these are all substances found in blood that contains nitrogen

  Nonprotein nitrogen
• these substances arise from the breakdown of proteins and nucleic acids
• NPN - measurements monitor and assess renal function
• originated from the past where removal of protein (PFF) is requirement before analysis

  NPN
• • Urea (45-55%)
  • Amino Acids (20%)
  • Uric Acid (20%)
  • Creatinine (5%)
  • Creatine (1-2%)
  • Ammonia (0.2%) - neurotoxic


  NPN Components
• (CO[NH2]2)


  Urea Formula
• • major excretory product of protein and amino acid catabolism
  • synthesized in the liver from CO2 and NH3 arising from deamination of AA

  Urea
• • Kidneys - as it is readily filtered by the glomerulus but 40-60% is passively reabsorbed by collecting duct if blood concentration is increased
  • GI tract and skin - less than 10%


  Urea is excreted by
• Protein - Amino Acids - Ammonia - Urea
• • urea measurement
  • assay for urea based on nitrogen content
  • assessment of nitrogen balance for nutritional management

  Blood Urea Nitrogen
• • Azotemia - elevated urea in blood
  • Uremia / Uremic syndrome - very high levels of plasma urea accompanied by renal failure


  INCREASED LEVELS of urea
• 1. Pre renal changes
  2. Renal changes
  3. Post renal changes


  Uremia / Uremic syndrome is caused by
• 1. decreased blood flow to kidneys - reduced blood flow - less urea to the kidney - less urea is filtered
  2. level of protein metabolism - high protein diet (ketogenic)
  3. increased protein catabolism

  Increased levels: Pre renal changes

  *plasma CREA is normal
• • acute / chronic renal failure
  • glomerulonephritis
  • tubular necrosis
  • other intrinsic renal disease

  Increased levels: Renal changes

  *plasma CREA is increased
• due to urine flow obstruction caused by tumors of the bladder

  Increased levels: Post-renal changes
• Decreased levels:

  -severe vomiting and diarrhea

  -increased protein synthesis such as pregnancy and infancy
• 10:1 or 20:1


  helps in differentiation of the cause of abnormal urea concentration

  BUN/CREA ratio
• • pre-renal conditions: CREA is normal
  • CHI (congenital hyperinsulinism)
  • increased protein breakdown

  elevation in BUN than CREA
• • post renal conditions

  BUN/CREA ratio with an elevated creatinine
• • decreased urea production
  • low protein intake
  • acute tubular necrosis
  • sever liver disease

  Decreased BUN/CREA ratio
• • made in the liver and pancreas from AA (Arginine, Lysine, Methionine)
  • used as energy source by the muscles

  Creatine
• • Muscular dystrophy
  • Poliomyelitis
  • Hyperthyroidism
  • Trauma

  Increased Creatine

  *but normal creatinine level
• • anhydrose form of creatine
  • end product of normal muscle catabolism
  • proportional relationship between muscle mass and rate of release into the blood
  • readily filtered by glomerulus, not reabsorbed by tubules

  Creatinine
• Creatinine is used to determine completeness of 24-hour urine collection
• • reflects relative muscle mass, the rate of creatinine turnover, and renal function
  • more specific but less sensitive monitor of renal fx
  • not affected by diet

  Plasma concentration
• • decreased glomerular filtration and urinary tract obstruction

  Increased levels of creatinine
• Creatinine Clearance

  -plasma concentration of creatinine and creatinine clearance is inversely proportional

  -is a relatively insensitive marker and may not be measurably increased
• end product of complete purine catabolism

  Uric Acid
• purines are converted into uric acid and transported into plasma


  Liver
• form found in plasma (pH 7.4)

  MSU (monosodium urate)
• form found in urine (pH 5-7.5)

  Uric Acid
• • Liver
  • Kidney
  • Bread
  • Shellfish
  • Beans
  • Herrings
  • Sardines
  • Legumes

  Purine rich foods
• highly susceptible to the development of renal calculi

  Gout
• deposits of urate levels form in tissue causing deformities

  Tophi
• Adenosine - Inosine - Xanthine - Guanine - Uric acid
• -caused by complete deficiency in enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT)


  Lesch-Nyhan Syndrome
• • secondary to liver disease and defective tubular reabsorption as in fanconi
  • caused by chemotherapy with 6-mercaptopurine or azathioprine as well as overtreatment with allopurinol

  Decreased levels of Uric Acid
• • product of deamination of AA and metabolic
  • consumed by parenchymal cells
  • measurement of urine ammonia

  Ammonia
• preceded by a viral infection that is often treated with aspirin and can be fetal


  Reye's syndrome
• ammonia is not removed from circulation and blood conc increases

  Liver failure