Chem: Section 4.2- Non-Protein Nitrogen Compounds

What is the calculation for creatinine clearance?

urine creatinine x volume x average surface area (1.73)

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plasma creatinine x time (1440min) x pt surface area

answer is mL/min

**if you are not given the body surface area, remove the average SA and body SA from equation

formula used for measuring creatinine clearance in pediatric patients

Schwarz formula

formula used for measuring creatinine clearance in adults over the age of 18, accounts for age

Cockcroft and Gault formula

Where does creatinine come from?

waste product of creatine and phosphocreatine, from muscle breakdown

How is creatinine metabolized?

once creatinine enters the blood supply from the muscle, it travels to kidneys where it is then excreted

How is creatinine excreted?

excreted almost completely through the urine

Where does Cystatin C come from?

produced by all nucleated cells at a constant rate

How is Cystatin C metabolized?

filtered by kidneys but almost completely reabsorbed and metabolized by proximal renal tubules

Is Cystatin C excreted in the urine?

No, it is almost completely reabsorbed

How is urea produced?

protein → amino acids → ammonia + CO2 → urea + water

synthesized in the liver

How is BUN measured? enzyme and product measured

enzyme: urease

product measured: ammonium ion (goes on to Berthelot)

Berthelot reaction that uses nitroprusside

Measures indophenol which is directly prop to BUN

Colorimetric method uses diacetyl monoxime

What will interfere with BUN measurement?

gray and light blue tubes inhibit

How is BUN metabolized?

filtered through glomerulus, almost half (50%) is reabsorbed back into the blood by passing through the nephron tubule

How is BUN excreted?

in urine, is the most abundant waste product in the urine

In the chemical method, creatinine reacts with ________________ in an (acidic/alkaline) environment to generate an orange-red product.

Creatinine reacts with *picric acid* in an *alkaline* environment to generate a orange-red product

What are some interferences for the chemical method of creatinine testing?

not specific for creatinine- orange-red color can be generated by protein, glucose, ascorbic acid, acetone, acetoacetate, pyruvate, guanidine and cephalosporins.

Also anything that adds color will show positive (bilirubin, hemolysis)

What 3 enzymes can be used to produce product in the enzymatic creatinine testing method?

1) creatininase

2) creatinase

3) creatinine deaminase

Why is the enzymatic creatinine testing method less susceptible to interference from keto acids and cephalosporin antibiotics?

because it measures a colorless product

What are some advantages of measuring Cystatin C levels over creatinine clearance levels when assessing GFR?

it is unaffected by muscle mass, sex, age, diet, ethnicity

capable of measuring small amounts of a disease present

measurable amounts in all body fluids except urine

As GFR decreases, what happens to cystatin C?

increases (in blood)

How is the BUN:creatinine ratio used in the assessment of renal status?

it is useful in distinguishing between various causes of a reduced GFR

What conditions are associated with a low BUN:creatinine ratio? (e.g. 5:1)

anything that causes a low BUN:

acute nephron tubular necrosis, low protein intake (malnutrition), starvation, severe liver disease

What conditions are associated with an increased BUN:creatinine ratio with a normal creatinine? (e.g. 30:1)

pre-renal uremia, high protein intake in the diet, GI tract hemorrhage

What conditions are associated with an increased BUN:creatinine ratio with a high creatinine level? (e.g. 30:10)

neither excreted properly:

obstruction of urinary track or end-stage renal disease

What does an increase in creatinine without an increase in BUN mean?

is very rare, probably a lab error

What is the Gold Standard Method for all clearance tests?

inulin

What two specimens are required for a creatinine test?

24 hour urine plus a blood test taken before, during, or within 24 hours after the urine is collected

Are uremia and azotemia the same?

No, uremia and azotemia are sometimes used interchangeably but uremia generally indicates a toxic condition while azotemia may indicate an increase in non-protein nitrogen substances in the blood before symptoms appear.

What are the 3 chemicals used to precipitate proteins with the turbidimetric method of measuring microalbuminuria?

*sulfosalicylic acid (SSA)*, trichloroacetic acid, benzethonium chloride

What are the dye-binding chemicals used to measure urinary albumin?

methyl orange, bromcresol green (BCG), bromcresol purple (BCP)

What are the two purine nucleosides that uric acid is derived from?

adenosine and guanosine

What is the enzyme and product measured in the enzymatic method of measuring uric acid?

enzyme: *uricase*

product measured: can measure *allatoin* or *hydrogen peroxide* can go into a second reaction to produce a chromagen

What are some interferences for the enzymatic method of measuring uric acid?

False increase: excessive amounts of protein and lipids, hemoglobin and bilirubin add color

False decrease: Xanthine is a competitive inhibitor to uricase enzyme

What are the chemicals involved in the colorimetric method of measuring uric acid?

phosphotungstic acid and sodium carbonate (Na2CO2)

What is the pH of the colorimetric method of measuring uric acid? (acidic or alkaline)

alkaline

What can interfere with colorimetric testing for uric acids? What are some false increases and decreases?

proteins can interfere so sample must be a protein-free filtrate

false increase: glucose, ascorbic acid, glutathione, hemoglobin, drugs such as acetaminophen

false decrease: caffeine (similar to Xanthine, is a competitive inhibitor)

What can cause uric acid to be increased?

anything that causes increased cellular turnover-- leukemia, hemolysis, rhabdo

What can cause hyperuricemia?

- over production of proteins

- renal retention of uric acid

- acidemia

- defect in the purine salvage pathway (e.g. Lesch-Nyhan syndrome)

What condition can present with hyperuricemia?

Lesch-Nyhan syndrome: deficiency of a transferase enzyme in the purine salvage pathway

What conditon is associated with Lesch-Nyhan syndrome?

Tophi: deposits of urates in subcutaneous tissue and brain; if it gets in the brain patients can have self-destructive tendencies

What can cause hypouricemia?

- reduced purine synthesis

- defective reabsorption of uric acid in the kidney (e.g. Fanconi's)

What condition can present with hypouricemia?

Fanconi's disease: a disorder of the proximal tubule of the nephron, resulting in poor transport

Why must microalbuminuria testing be very sensitive?

the dipstick is not sensitive enough to pick microalbuminuria, that is also why it is sometimes referred to as "dipstick negative albumin"

How is uric acid metabolized?

almost completely reabsorbed in the proximal tubules

How is uric acid excreted?

urine

less acidic: urates

more acidic: uric acid crystals