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Non protein nitrogen compounds  Pathophysiology

- Decreased Concentration:
Low protein intake (inc. osmolality), Severe vomiting (dec.
osmolality) and diarrhea, Liver disease and Pregnancy
___________________________________________________
2. Uric Acid
 Physiology
- Major end-product of purine catabolism.
- Present as monosodium urates in plasma (98-100%
reabsorbed)
- May precipitate in tissues (blood pH ≈ 7; BUA > 6.8 mg/dL )
 Clinical application
- Inherited disorders of purine metabolism
- Gout
- Renal calculi
- Uric acid nephropathy (chemotheraphy)
1. UREA - Kidney dysfunction
 Physiology  Methods
- Major waste product of the protein catabolism
- Expressed as urea nitrogen (BUN)
- Affected by diet, metabolism and hydration
- Excreted by the kidneys
- Formed in the liver
 Clinical application
- Renal function, Hydration status, Nitrogen balance, Renal
disease, Adequacy of dialysis
- Conversion:
BUN X 2.14 = UREA
UREA X 0.467 = BUN
mg/dL x 0.357 = mmol/L
 Methods of Analysis

 Reference intervals
Child
- Plasma or serum: 2.0 – 5.5 mg/dL
Adult Female
- Plasma or serum: 2.6 – 6.0 mg/dL
Adult Male
- Plasma or serum: 3.5 – 7.2 mg/dL
Adult
- Urine, 24 hours: 250-750 mg/day
 Specimen requirements
- Heparinized plasma, serum or urine
- Lipemia, bilirubin, hemolysis (↓ UA)
- Salicylates and thiazides (↑ UA)
 Reference intervals
 Pathophysiology
Adult
Hyperuricemia (Enzyme deficiencies)
- Plasma or serum: 6 – 20 mg/dL
1. Lesch-Nyhan syndrome
- Urine, 24 hours: 12-20 g/day
↓ HGPRT
 Specimen Requirement
↓ reutilization of purine, ↑ synthesis of purine
- Use fasting blood
2. Glycogen storage disease type 1
- Avoid sodium fluoride or sodium citrate anticoagulants
↓ G-6-P
- Refrigerate Samples
↑ triglycerides, ↓ renal urate excretion
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3. Fructose intolerance  Reference intervals
↓ F1PA Child
↑ lactate, ↓ renal urate excretion - Plasma or serum: 0.3 – 0.7 mg/dL
4. Hemolytic and proliferative process Adult Female
↑ metabolism of cell nuclei - Plasma or serum: 0.6 – 1.1 mg/dL
5. Treatment of myeloproliferative disease w/ cytotoxic - Urine, 24 hours: 600 – 1,800 mg/day
drugs Adult Male
↑ destruction of cell - Plasma or serum: 0.9 – 1.3 mg/dL
6. Chronic renal disease - Urine, 24 hours: 800 – 2,000 mg/day
↓ uric acid filtration and secretion BUN / Creatinine Ratio : 10:1 to 20:1
7. Toxemia of pregnancy and lactic acidosis  Specimen requirements
↑ binding to renal tubules
8. Purine-rich diet
Hypouricemia
1. ↓ PRPP Synthetase
↓ de novo purine synthesis
2. Liver disease
↓ uric acid synthesis
3. Fanconi sydrome
Defective tubular reabsorption  Pathophysiology
4. Chemotheraphy with azathioprine or 6- - Increased Concentration:
mercaptopurine Renal failure (glomerular function)
↓ de novo purine synthesis ↑ Plasma Concentration = ↓ GFR
5. Overtreatment with allopurinol ________________________________________________________
↓ XO, ↓ de novo purine synthesis 4. Ammonia
___________________________________________________  Physiology
3. Creatinine - Increases in newborn
 Physiology - By product of amino acid deamination.
- Chief product of muscle metabolism - Converted to urea in the liver.
- Not affected by protein diet  Clinical application
 Clinical application - Hepatic failure and hepatic coma
- Sufficiency of kidney function - Reye’s syndrome
- Severity of kidney damage - Inherited deficiencies of urea cycle
- Progression of kidney disease - Conversion:
- Completeness of 24-hour urine Ammonia: 17g/mol
Glomerular filtration rate (Creatinine clearance) 88.4 NH3, 0.556 Glucose
- Volume of plasma filtered (V) by the glomeruli per unit of  Methods
time (mL/minute

- Example:

 Reference intervals
Child
- Plasma or serum: 68-136 µg/dL
 Methods Adult
- Plasma or serum: 19-60 µg/dL
 Specimen requirements
- Heparinized and EDTA tubes
- Samples is centrifuged at 0-4°C within 20 mins. of
collection and the plasma/serum removed
- Avoid cigarette smoking for several hours

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