Unit 4.2 - NPN (Uric Acid) Flashcards
Product of catabolism of purines bases (adenine & guanine).
Uric acid
Readily filtered by glomerulus but undergoes reabsorption and secretion.
Uric acid
Uric acid is 98-100% reabsorbed in the:
proximal convuluted tubule
<1% of uric acid is excreted in the:
distal tubules
70% of uric acid is excreted in the:
renal
30% of uric acid is excereted in the:
GI
Uric acid is relatively insoluble in plasma as monosodium urate at pH of:
7 pH
At concentration of >6.8 mg/dL, plasma is saturated ____ may form in the tissues.
urates crystals
At what pH does uric acid crystals may form?
<5.75 pH
High concentrations accumulate in the joints and tissue resulting in inflammation:
gouty arthritis
Uric acid measurement is used to: (5)
- confirm diagnosis and monitor treatment of gout;
- assess and prevent uric acid nephropathy during chemotherapeutic management;
- assess inherited disorders of purine metabolism;
- detect kidney dysfunction; and
- assist in the diagnosis of renal calculi.
T/F:
Decrease age, decrease waste substance.
True
intake of internal organs = rich in uric acid
T/F:
Uric acid nephropathy is common in cancer patients, resulting of rapid breakdown of cells, leading to hyperuricidemia.
True
T/F:
Uric acid causes damages to the organs, especially kidneys.
True
Uric acid pathophysiology:
Increased: hyperuricemia _ mg/dL
Greater than 6mg/dL
Happens in male between 30 and 50 years of age; in female, they appear after menopausal
Gout
Gout:
Patients have pain and inflammation of the joints caused by:
precipitation of sodium urates
Gout:
In hyperuricemia, __% of patients results of overproduction of uric acid.
25-30%
Gout:
Formation of:
renal calculi
Pathophysiology:
Uric acid is increased in nuclear breakdown, and is usually seen in patient undergoing: (4)
- chemotherapy for leukemia
- lymphoma
- multiple myeloma
- polycythemia
Uric acid is monitored to avoid:
nephrotoxicity
Pathophysiology:
This enzyme prevents the formation of uric acid and is slow acting.
Xantine oxidase
Pathophysiology:
Treatment to inhibit xantine oxidase.
Allopurinol
Pathophysiology:
This enzyme is given for managing uric acid, fast-acting, and at risk of developing methemoglobinuria.
Urate oxidase rasburicase
Fill in the blank:
Purine catabolism → Hypoxanthine → Xanthine → Uric acid → ___
Allantoin
T/F:
Allantoin is readily excretable and is water soluble in urinary excretion.
True
Pathophysiology:
Causes of kidney diseases:
Impaired filtration and secretion
T/F:
Nearly all of the uric acid in the plasma is present as monosodium urate and at pH less than 5.75 acid crystals may form in the urine.
T
T/F:
98-100% of uric acid reabsorption from glomerular filtrate occurs at the distal tubules
F
should be at the proximal convoluted tubules.
T/F:
Hyperuricemia may be exacerbated by a purine-rich diet, drugs, alcohol, and genetic variations
T
T/F:
Tophi may cause deformities due to crystalline uric acid and urate deposition and may also manifest in proliferative disorders
T
An X-linked genetic disorder only seen in males.
Lesch-Nyhan Syndrome
Lesch-Nyhan Syndrome is caused by the complete deficiency of what enzyme?
hypoxanthine-guanine-phosphoribosyltransferase (HPRT)
The lack of this enzyme prevents the reutilization of purine bases in the nucleotide salvage pathway. What enzyme is this?
hypoxanthine-guanine-phosphoribosyltransferase (HPRT)
Lesch-Nyhan:
It consequentially results in _ (increased, decreased) concentrations of uric acid (plasma and urine).
increased
What are the chacterization of Lesch-Nyhan Syndrome?
- Neurologic symptoms
- Mental retardation
- Self-mutilation
Lesch-Nyhan Syndrome:
_ (increased, decreased) purine synthesis, _ (increased, decreased) the degradation product
increases, increases
What are the other conditions with increased Uric Acid? (3)
- Mutations on phosphoribosylpyrophosphate synthetase
- Toxemia on pregnancy
- Lactic acidosis (competition for binding sites in renal tubules)
Causes of hyperuricemia: (8)
- Increased dietary intake of purine rich food
- Increased urate production (postmenopausal women, increased tissue catabolism such as in starvation)
- Decreased excretion
- Catabolic pathways enzyme defects
- Increased metabolism of cell nuclei (lymphoma, leukemia, multiple myeloma, polycythemia, hemolytic and megaloblastic anemia)
- Inherited disorders with enzyme deficiency (Lesch-Nyhan Syndrome)
- Decreased uric acid excretion (preeclampsia, lactic acidosis)
- Chronic renal disease (impaired filtration and secretion)
- Secondary to severe liver disease
- ↓ urea, ↓ uric acid
Hypouricemia
Hypouricemia
_ is a defective tubular reabsorption.
Fanconi’s syndrome
Hypouricemia occurs in chemotherapy with _ or _ (inhibits de novo purine synthesis)
6 mercaptopurine or azathiopurine
Hypouricemia happens when _ is overtreated.
allopurinol
Analytical methods:
Direct REDOX Method
Caraway/Henry’s Method
Analytical methods:
Uric acid + phosphotungstic acid + O 2 - - NaCO 3/OH- → tungsten blue + allantoin + CO 2
Caraway/Henry’s Method
Analytical methods:
Product of Caraway/Henry’s Method:
tungsten blue
Analytical methods:
Based on the oxidation of UA in PFF and reduction of PTA
Caraway/Henry’s Method
Analytical methods:
Interferences on Caraway/Henry’s Method: (5)
False (+) / increased in:
* turbidity
* aspirin and metabolite
* acetaminophen
* caffeine
* theophylline
Analytical methods:
Iron reduction method reduces ferric ion to ferrous ion using what?
Ligand
Analytical methods:
Product of Iron Reduction Method:
ferrous ion + chromophore
Analytical methods:
Conversion of uric acid to allantoin using uricase.
Enzymatic methods
Enzymatic methods of uric acid:
This method measures differential absorption of UA and allantoin at 290-293 nm.
Uricase Method (Blauch and Koch)
Enzymatic methods of uric acid:
Advantage of Uricase Method (Blauch and Koch): (1)
more specific = NEEDS SPECTROPHOTOMETRY!
Enzymatic methods of uric acid:
Disadvantages of Uricase Method (Blauch and Koch): (2)
- protein cause high background absorbance
- negative interference due to Hb and xantine
T/F:
Negative interference in Uricase Method is caused by hemolysed sample, causing the release of Hgb.
True
Enzymatic methods of uric acid:
UA + O2 + 2 H2O → allantoin + CO2 + H2O2
Uricase method (Blauch and Koch)
Enzymatic methods of uric acid:
- UA + O2 + 2 H2O → allantoin + CO2 + H2O2
- H2O2 + indicator dye → colored compound + 2 or 3 H2O
Coupled Enzymatic Method
Enzymatic methods of uric acid:
Disadvantage of couplez enzymatic method:
Bilirubin and ascorbic acid may destroy peroxide
Falsely decreased: reducing agent, inhibiting glucose oxidase
Enzymatic methods of uric acid:
Remedy in preventing the false decrease of bilirubin and ascorbic acid in coupled enzymatic method.
addition of potassium ferricyanide and ascorbate oxidase
Reference method in Uric Acid Determination:
IDMS
Specimen requirements in Uric Acid:
heparinized plasma, serum, or urine
green top! :)
T/F:
Diet may affect uric acid concentration.
True
T/F:
Gross lipemia should be avoided.
T
T/F:
hemolysis, with concomitant glutathione release, may result in HIGH values.
T
What are the 2 enzymes that increases the values for uric acid?
- Salicylates
- Thiazides
Serum sample may be stored refrigerated for _ to _ days.
3-5 days
What tubes should not be used in measuring Uric Acid?
EDTA Tube (Lavender)
Sodium Fluoride (Gray)
Urine specimen in measuring UA should be _ and has a pH of _.
alkaline; pH 8
Reference intervals of plasma/serum for male:
3.5-7.2 mg/dL
Reference intervals of plasma/serum for female:
2.6-6.0 mg/dL
Reference intervals of plasma/serum for child:
2.0-5.5 mg/dL
Reference intervals of 24-hour urine for adult:
250/750 mg/day
What is the methodology for UA determination is free of interferences and considered reference?
IDMS
