315 nonprotein nitrogen compounds

what is the major exretory product of protein and amino acid catabolism

urea

what percentage of blood NPN is urea

about 75%

which NPN is found in the highest concentration in blood

urea

how is urea transported and excreted

water soluble, transported via blood to kidneys - excreted in urine

what releases nitrogen during protein metabolism

ammonia

which cycle converts ammonia to urea

the urea cycle (krebs cycle of urea)

outline the excretory pathway of urea

protein metabolism → ammonia → urea cycle → blood → kidneys → urine

what is azotemia

increased blood urea

what is uremia

severe increase in urea with symptoms

what is the primary clinical application of urea testing

assess renal function

what are two additional uses of urea testing

monitoring hydration status and nitrogen balance

in what form is urea often evaluated clinically

as blood urea nitrogen

what is the main analytical method for urea

enzymatic urease method

describe the urease method for urea measurement

urease hydrolysis urea → ammonia + carbonate → ammonia reacts with gldh → nadh oxidized → decreased absorbance measured

what are the prerenal causes of elevated urea

low renal blood flow

what are the renal causes of elevated urea

intrinsic kidney damage

what are the postrenal causes of elevated urea

urinary obstruction

what is the end product of purine metabolism

uric acid

which purines are metabolized to uric acid

adenine and guanine

where is uric acid synthesized

in the liver, from dietary nucleic acids an endogenous nucleic acid turnover

how is uric acid handled in the kidney

filtered by the glomerulus, mostly reabsorbed in proximal tubules

in what form does uric acid exist in plasma

monosodium urate (low solubility)

what disease is confirmed and monitored using uric acid testing

gout

why is uric acid measured in oncology patients

to monitor for tumor lysis syndrome and uric acid nephropathy during chemotherapy.

which inherited disorder can be diagnosed/monitored with uric acid testing

lesch-nyhan syndrome (purine metabolism defect)

what renal conditions are associated with elevated uric acid

renal calculi (stones) and kidney dysfunction

what is the most common method for uric acid measurement

uricase method

describe the uricase method

uricase converts uric acid → allantoin + hydrogen peroxide

how are coupled enzymatic assays used in uric acid testing

they measure h2o2 generated in the uricase reaction

what detection methods are used for uric acid assays

colorimetric, spectrophotometric, chemiluminescent

what can interfere with uric acid assays

hemolysis and high billirubin

what is hyperuricemia

elevated uric acid levels

what are two main causes of hyperuricemia

overproduction (excess nucleic acid catabolism) and underexcretion (renal impairment)

where is creatine synthesized and from which amino acids

in the liver from arginine, glycine, methionine

how is creatine transported and activated in muscle

transported to muscle → phosphorylated by creatine kinase → creatine phosphate

how is creatinine formed

spontaneous, irreversible conversion of creatine/phosphate

how is creatinine handled in the body

released into blood and excreted in urine

what is the relationship between creatinine production and muscle mass

constant production, proportional to muscle mass

why is creatinine a more reliable renal marker than urea

its less affected by diet/protein intake

what does plasma creatinine concentration reflect

muscle mass, creatine turnover, and renal excretion

what is the primary clinical use of creatinine

marker of renal function

what does creatinine clearance reflect

glomerular filtration rate (GFR)

what is the formula for creatinine clearance (CrCl)

(Urinecreatinineconcentration×Urinevolume)

÷(Plasmacreatinineconcentration×Collectiontime)

what is the classic method for creatinine measurement

jaffe reaction (rate measurement reduces interference)

what is the advantage of enzymatic methods for creatinine

greater specificity

what modern method measures creatine accurately

high performance liquid chromatography (HPLC)

what does elevated plasma creatinine indicate

renal dysfunction

when does plasma creatinine rise in renal disease

after 50% of renal function is lost (late indicator)

what does elevated plasma creatine (not creatinine) suggest

muscle disorders

are plasma creatine and urinary creatinine elevated in renal disease

no, creatine elevations are associated with muscle disorders, not renal disease

how is ammonia produced in the body

during amino acid catabolism and intestinal bacterial metabolism

how is ammonia removed from circulation

by the liver via the urea cycle

how is ammonia excreted by the kidneys

as ammonium ion which also buffers urine pH

why does hepatic failure cause hyperammonemia

impaired urea cycle prevents ammonia detoxification

what pediatric condition is associated with hyperammonemia

reyes syndrom

what do inherited urea cycle enzyme deficiencies cause

severe neonatal hyperammonemia

what is the clinical effect of elevated ammonia

neurotoxicity (neurological symptoms)

what are challenges in ammonia measurement

low concentration instability, high concentration risk

what specimen requirements arecritical for ammonia testing

avoid hemolysis, collect in edta or heparic tube, keep sample on ice

what is the most common enzymatic assay for ammonia

gldh assay

how does the gldha assay measure ammonia

ammonia + α-ketoglutarate → glutamate with oxidation of NADPH → decreased absorbance at 340 nm.

what condition results from elevated ammonia

hyperammonemia

why is ammonia considered neurotoxic

high levels cause CNS effects

what are clinical manifestations of hyperammonemia?

confusion, tremor, seizures, coma