Non protein nitrogen
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The document discusses non-protein nitrogen (NPN) substances measured in clinical chemistry to evaluate renal function. It focuses on blood urea nitrogen (BUN), creatinine, uric acid, and ammonia. BUN, creatinine, and uric acid are produced from protein or nucleic acid breakdown, while ammonia is produced from amino acid metabolism. Increased levels of these NPNs can indicate renal or hepatic impairment. Creatinine is the most useful marker for glomerular filtration rate and renal function since it is not reabsorbed and its production rate is constant.
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Non protein nitrogen
- 1. 1 CLINICAL CHEMISTRY NON - PROTEIN NITROGEN Presented by: Shahid Nawaz Researcher King Saud University Riyadh
- 2. 2 Introduction • NPN ( Non - Protein Nitrogen ) is a “funky” term that can be used for a bunch of different substances that have the element nitrogen in them, but are not proteins. • This is a little unusual, because most of the body’s nitrogen is associated with proteins. • There are many different unrelated NPNs, but we are only interested in 4 of them: • Creatinine , Blood Urea Nitrogen ( BUN ) , Uric Acid and Ammonia • In general, plasma NPNs are increased in renal failure and are commonly ordered as blood tests to check renal function
- 3. 3 Key Terms • Allantoin • Ammonia • Azotemia • BUN / Creat Ratio • Creatinine Clearance • Creatine • Creatinine • GFR • Glomerulus • Gout • Hyper ( hypo ) uricemia • NPN • Pre-renal • Post- renal • Purines • Renal absorption • Renal secretion • Uric acid • Urea • Uremic syndrome • Reyes Syndrome
- 4. 4 Objectives • List the origin and principle clinical significance of BUN, Creatinine, Uric Acid and Ammonia • List the reference ranges for the 4 principle NPNs • Discuss why creatinine is the most useful NPN to evaluate renal function • Calculate Creatinine Clearance • Discuss the common methodologies used to measure BUN, Creatinine, Uric Acid and Ammonia
- 5. 5 • General ideas about the NPNs • Antiquated term when protein – free filtrates were required for testing • The NPNs were used for evaluating renal function • The NPNs include about 15 different substances • Most NPNs are derived from protein or nucleic acid catabolism • Most important NPNs – BUN ( Blood Urea Nitrogen ) – Creatinine – Uric acid – Ammonia
- 6. 6 • BUN ( Blood Urea Nitrogen )BUN ( Blood Urea Nitrogen ) – Blood Urea Nitrogen = BUNBUN = Urea – 50% of the NPNs – Product of protein catabolism which produces ammonia – Ammonia is very toxic – converted to urea by the liver – Liver converts ammonia and CO2 – Filtered by the glomerulus but also reabsorbed by renal tubules ( 40 % ) – Some is lost through the skin and the GI tract ( < 10 % ) – Plasma BUN is affected by • Renal function • Dietary protein • Protein catabolism Urea
- 7. 7 – BUN disease correlationsBUN disease correlations • Azotemia = Elevated plasma BUN • PrerenalPrerenal ↑↑ BUNBUN ( Not related to renal function ) – Low Blood Pressure ( CHF, Shock, hemorrhage, dehydration ) – Decreased blood flow to kidney = No filtration – Increased dietary protein or protein catabolism • PrerenalPrerenal ↓↓ BUNBUN ( Not related to renal function ) – Decreased dietary protein – Increased protein synthesis ( Pregnant women , children )
- 8. 8 – RenalRenal causes ofcauses of ↑↑ BUNBUN • Renal disease with decreased glomerular filtration – Glomerular nephritis – Renal failure form Diabetes Mellitus – Post renalPost renal causes ofcauses of ↑↑ BUN ( not related to renal function )BUN ( not related to renal function ) • Obstruction of urine flow – Kidney stones – Bladder or prostate tumors – UTIs
- 9. 9 • BUN / Creatinine RatioBUN / Creatinine Ratio – Normal BUN / Creatinine ratio is 10 – 20 to 1Normal BUN / Creatinine ratio is 10 – 20 to 1 – Creatinine is another NPNCreatinine is another NPN – Pre-renal increased BUN / Creat ratio – BUN is more susceptible to non-renal factors – Post-renalPost-renal increased ratio BUN / Creat ratio – Both BUN and Creat are elevated – RenalRenal decreased BUN / Creat ratio – Low dietary protein or severe liver disease Increased BUN Normal Creat Increased BUN Increased Creat Decreased BUN Normal Creat
- 10. 10 – BUN analytical methodsBUN analytical methods • BUN is an old term, but still in common useBUN is an old term, but still in common use • Specimen : Plasma or serum • To convert BUN to Urea : BUN x 2.14 = Urea ( mg / dl ) UREA 2 NH4 + + HCO3 - Urease NH4 + + 2-OXOGLUTARATE GLDH GLUTAMATE NADH NAD Measure the rate of decreased absorbance at 340 nm NADH absorbs … NAD does not absorb Reference range : 10 – 20 mg / dl
- 11. 11 • CREATININE Liver Amino Acids Creatine Muscles Creatine Phosphocreatine Muscles Phosphocreatine Creatinine Creatinine formed at a constant rate by the muscles as a function of muscle mass Creatinine is removed from the plasma by glomerular filtration Creatinine is not secreted or absorbed by the renal tubules Therefore : Plasma creatinine is a function of glomerular filtration Unaffected by other factors It’s a very good test to evaluate renal function
- 12. 12 – Creatinine disease correlations • Increased plasma creatinine associated with decreased glomerular filtration ( renal function ) • Glomerular filtration may be 50 % of normal before plasma creatinine is elevated • Plasma creatinine is unaffected by diet • Plasma creatinine is the most common test used to evaluate renal function • Plasma creatinine concentrations are very stable from day to day - If there is a delta check , its very suspicious and must be investigated
- 13. 13 – Creatinine analytical techniques • Jaffee Method ( the Classic technique ) Creatinine + Picrate Acid Colored chromogen Specimen : Plasma or serum Elevated bilirubin and hemolysis causes falsely decreased results Reference range : 0.5 - 1.5 mg / dl
- 14. 14 • URIC ACID – Breakdown product of purines ( nucleic acid / DNA ) – Purines from cellular breakdown are converted to uric acid by the liver – Uric acid is filtered by the glomerulus ( but 98 – 100 % reabsorbed ) – Elevated plasma uric acid can promote formation of solid uric acid crystals in joints and urine
- 15. 15 – Uric acid diseases • Gout – Increased plasma uric acid – Painful uric acid crystals in joints – Usually in older males ( > 30 years-old ) – Associated with alcohol consumption – Uric acid may also form kidney stones • Other causes of increased uric acid – Leukemias and lymphomas ( ↑ DNA catabolism ) – Megaloblastic anemias ( ↑ DNA catabolism ) – Renal disease ( but not very specific )
- 16. 16 – Uric acid analysis Uric acid + O2 + H2O Allantoin + CO2 Uricase Uric acid absorbs light @ 293 nm , Allantoin does not. The rate of decreased absorption is proportional to the uric acid concentration. Specimen : Plasma or serum + H2O2 Reference range : 3.5 - 7.2 mg/dl (males) 2.6 - 6.0 mg/dl (females) Let’s remember 3.0 - 7.0 mg/dl
- 17. 17 • AMMONIA – Produced from the deamaination of amino acids in the muscle and from bacteria in the GI tract – Ammonia is very toxic - The liver converts ammonia into urea – Urea is less toxic and can be removed from the plasma by the kidneys – In severe hepatic disease, the liver fails to convert ammonia into urea, resulting in increased plasma ammonia levels – Increased plasma ammonia concentrations in : • Liver failure • Reye’s Disease
- 18. 18 Ammonia analytical techniques NH4 + + 2-OXOGLUTARATE + NADPH L-GLUTAMATE + NADP+ There is a decreasing absorbance @ 340 nm, proportional to the ammonia concentration. Specimen : EDTA or Heparinized Whole Blood on ice Must be tested ASAP or plasma frozen Delayed testing caused false increased values Reference range : 20 – 60 µg / dl
- 19. 19 • Creatinine Clearance – Calculated measurement of the rate at which creatinine is removed from the plasma by the kidneys – Measurement of glomerular filtration ( renal function )Measurement of glomerular filtration ( renal function ) – A good test of glomerular filtration because • Creatinine is an endogenous substance ( not affected by diet ) • Creatinine is filtered by the glomerulus, but not secreted or re-absorbed by the renal tubules
- 20. 20 24 Hour Urine collection Container. The volume can be measured directly off the container.
- 21. 21 – Creatinine Clearance specimens • 24 hour urine specimen • Plasma / serum creatinine collected during the urine collection • 24 Hour Creatinine Clearance Formula • CREATININE CLEARANCE = A U 73.1 P V U = Creatinine concentration of the 24 hour urine ( mg / dl ) V = 24 hour urine volume ( mls ) per minute - V / 1440 = mls / minuteper minute - V / 1440 = mls / minute P = Plasma creatinine concentration ( mg / dl ) A = Correction factor accounts for differences in body surface area obtained from a height – weight chart
- 22. 22 Example of a 24 Hour Creatinine Clearance calculation 24 hour urine volume = 1000 mls 24 hour urine creatinine = 20.0 mg / dl Plasma creatinine = 5.0 mg / dl Patients height / weight = 6’00 / 190 lbs ( see pg. 680 ) ( ) ( ) ( ) ( ) ( ) 100020.01.73 1.731440 5.0 2.05 UV Creat Cl P A = = = ÷ ÷ Creat Cl = 2 ml / min …. Very poor clearance !!!
- 23. 23 • Procedure for 24 Hour Urine Collection – Have the patient empty his / her bladder ( discard this urine ). – Note the time . For the next 24 hours, have the patient collect and save all urine in an appropriate container. – At the end of the 24 hour period have the patient void one last time into the urine container. This completes the collection. – If possible, keep the urine specimen refrigerated.
- 24. 24 – Reference range • 97 - 137 ml / min ( male) • 88 - 128 ml / min (female) • Let’s remember 90 - 130 ml / min
- 25. 25 NPN TOP 10 • Increased Creatinine associated with renal failure • Increased BUN associated with renal failure and protein catabolism • Increased Uric Acid associated with Gout • Increased Ammonia is associated with liver disease • Creatinine derived from cellular creatine … very constant from day to day • Delta checks on plasma Creatinine must be investigated !!! • BUN ( Urea ) is derived from protein catabolism • Protein Ammonia Urea • Uric Acid is derived from purine( a component of DNA ) catabolism • Decreased Creatinine Clearance associated with decreased Glomerular Filtration = AP UV 73.1 ClearanceCreatinine Don’t forget to divide V by 1440 !
- 26. 26 Reference Ranges • BUN 10 - 20 mg / dl • Creatinine 0.5 - 1.5 mg /dl • Uric Acid 3.0 - 7.0 mg / dl • Creatinine Clearance 90 - 130 ml / min • Ammonia 20 - 60 ug / dl • BUN / Creat Ratio 10 - 20 to 1