[2S] UNIT 4 Non-Protein Nitrogen Compounds: Urea & Uric Acid Flashcards
Nitrogen-containing substances found in blood that are not proteins.
Non-Protein Nitrogen Compounds
For the assessment and monitoring of renal function
Non-Protein Nitrogen Compounds
Prior to the current analytical methods available, nitrogen content was measured with the removal of proteins before analysis
Protein Free Filtrate
Most Abundant NPN
Urea
Least Abundant NPN
Ammonia
Derived from the catabolism of protein and amino acids
Urea
Major NPN found in the blood (45-50% of total NPN)
Urea
Synthesized in the liver from CO2 + ammonia
Urea
Filtered freely by the glomerulus
○ 40% Reabsorbed
○ 50% Excreted in the Urine
○ <10% Excreted through GI tract and skin
Urea
Arising from the deamination of the amino acids by means of the Krebs-Henseleit Cycle or Ornithine Pathway
Urea
T/F: The concentration of urea is dependent on renal function and perfusion, the protein content of the diet, and the amount of protein catabolism
T
CLINICAL APPLICATION
● Assess nitrogen balance
● Aid in the diagnosis of renal disease
● Verify the adequacy of dialysis
Urea
CLINICAL APPLICATION
● Evaluate renal function
● Determine hydration status
Urea
PATHOPHYSIOLOGY OF UREA
Fatal if not treated by dialysis or transplantation
Uremia / Uremic Syndrome
PATHOPHYSIOLOGY OF UREA
Very high levels of plasma urea accompanied by renal
failure
Uremia / Uremic Syndrome
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
↑ Creatinine ↑ B.U.N. ↑ Osm.
Pre-Renal
PATHOPHYSIOLOGY OF UREA
An elevated concentration of urea in the blood
Azotemia
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
Decreased blood flow to the kidneys
Pre-Renal
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
Impaired Perfusion: (Commonly seen in patients with)
○ Cardiac Failure (Congestive Heart Failure)
○ Sepsis (Shock)
○ Blood Loss (Hemorrhage)
○ Dehydration
○ Vascular Occlusion
Pre-Renal
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
Level of protein metabolism
■ High protein diet
■ Increased protein catabolism
Pre-Renal
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
● Occurs in the kidneys
● Decreased renal function
Renal / Intrinsic
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
● Small-vessel Vasculitis
● Acute Tubular Necrosis
Renal / Intrinsic
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
● Acute / Chronic Renal Failure
● Glomerulonephritis
Renal / Intrinsic
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
● Prolonged Hypotension
● Interstitial Nephritis
Renal / Intrinsic
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
Happens after reaching the kidneys
Post-Renal
High urea: Normal Creatinine
Pre-Renal
AZOTEMIA (BASED ON THE DYSFUNCTION OR SITE OF ABNORMALITY)
Urinary Tract Obstruction
○ Causes:
■ Renal calculi
■ Tumors of the bladder/prostate
■ Severe infection like UTI
Post-Renal
High urea: High Creatinine
Renal
Normal urea: High Creatinine
Post-Renal
Urea Nitrogen (B.U.N.) : Creatinine
10:1 to 20:1
Determination of urinary concentration is of value in the assessment of nitrogen balance for nutritional
management
BUN
Chemical Formula of Urea
CO(NH2)2
B.U.N. to Urea
2.14
B.U.N.. in mg/dL to mmol/L
0.357
Urea to B.U.N
0.467
UREA DETERMINATION
Measures urea as a whole without isolating nitrogen
Direct Method
UREA DETERMINATION
Measures the nitrogen content of urea (B.U.N.)
Indirect Method
UREA DETERMINATION
Uses:
○ Evaluate renal function
○ Assess hydration status
○ Determine nitrogen balance
○ Verify adequacy of dialysis
Indirect Method
UREA METHODS OF DETERMINATION
● Fearon’s Reaction
● Also known as Friedman’s Method or Xanthydrol Method
Condensation with Diacetyl Monoxime Method
UREA METHODS OF DETERMINATION
Reagents: strong acid, oxidizing agent, ferric ions,
thiosemicarbazide
Condensation with Diacetyl Monoxime Method
UREA METHODS OF DETERMINATION
Product of Condensation with Diacetyl Monoxime Method
Yellow Diazine Derivative
UREA METHODS OF DETERMINATION
Direct or Indirect?
Condensation with Diacetyl Monoxime Method
Direct
UREA METHODS OF DETERMINATION: ADVANTAGES
● Ammonia does not interfere in the measurement
● Used in auto analyzers
Condensation with Diacetyl Monoxime Method
UREA METHODS OF DETERMINATION: DISADVANTAGES
● Non-specific
● Uses toxic substances
Condensation with Diacetyl Monoxime Method
UREA METHODS OF DETERMINATION
DAM + water === (H+) diacetyl
Diacetyl + urea === (Fe+3) diazine
Condensation with Diacetyl Monoxime Method
UREA METHODS OF DETERMINATION
Urea + o-phthalaldehyde (H+) → isoindoline + naphthylethylene diamine (H+) → colored product
Reaction w/ O-phthalaldehyde and Naphthylethylene Diamine
UREA METHODS OF DETERMINATION
Product of Reaction w/ O-phthalaldehyde and Naphthylethylene Diamine
Chromogen / Colored Product
UREA METHODS OF DETERMINATION
Reaction w/ O-phthalaldehyde and Naphthylethylene Diamine
UREA METHODS OF DETERMINATION: ADVANTAGES
● No ammonia interference
○ Measure entire urea and do not isolate the nitrogen content
● Used in automation
Reaction w/ O-phthalaldehyde and Naphthylethylene Diamine
UREA METHODS OF DETERMINATION: DISADVANTAGES
Sulfa containing drugs
interfere
Reaction w/ O-phthalaldehyde and Naphthylethylene Diamine
UREA METHODS OF DETERMINATION
It is a 2-step procedure wherein we need to digest urea first; this allows the isolation of nitrogen component
Micro-Kjeldahl Method
UREA METHODS OF DETERMINATION
Direct or Indirect?
Micro-Kjeldahl Method
Indirect
UREA METHODS OF DETERMINATION
Digestion: urea (H2SO4 + H3PO4) → NH4+
○ Digestion is done by adding strong acids, eg.
sulfuric acid and phosphoric acid
○ Isolated content: ammonium
Micro-Kjeldahl Method