NON-PROTEIN NITROGENOUS COMPOUNDS 2 Flashcards by Unknown Unknown

metabolic waste product of purine metabolism

URIC ACID

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_______reabsorbed by PCT

98-100%

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URIC ACID

small amount are secreted by _______

DCT (Distal convoluted tubule)

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___________is formed from the breakdown of nucleic acids and in is an end product of purine metabolism

Uric acid

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__________ is transported by the plasma from the liver to the kidney, where it is filtered and where about ______ is excreted

Uric acid - 70%

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The remainder of uric acid is excreted into the _________

GI tract

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At concentrations greater than _______ the plasma is saturated

relatively insoluble (blood pH)
6.8 mg/dl

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Resulting to _____________

urate crystal formations

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Why measure uric acid?
(5)

To assess inherited disorders of purine metabolism
To confirm diagnosis and monitor treatment of gout
To assist in the diagnosis of renal calculi
To prevent uric acid and nephropathy during chemotherapeutic treatment
To detect kidney dysfunction

(5)

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In disease correlation there are three elevated Uric acid disease (3)

Gout
Increased catabolism of nucleic acids
Renal diseases

GIR

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-precipitation of sodium urates in the joints
cause hyperuricemia
prone to renal calculi
tophi formations (tissues)

Gout

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DISEASE CORRELATION

In patients with proliferative disorders on “chemotheraphy”

monitoring Uric acid level to avoid nephrotoxicity

leukemia
lymphoma
multiple myeloma
polycythemia

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treatment of proliferative disorders

TX: Allopurinol

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DISEASE CORRELATION
other renal disease:

hemolytic or megaloblastic anemia
lesch nyhan syndrome
glycogen storage disease
G-6-PD deficiency

HLGG

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Filtration and secretion are impaired

Chronic renal disease

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X linked genetic disorder
Complete deficiency of hypoxanthine guanine phosphoribosyltransferase

Lesch-Nyhan Syndrome

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Prevents reutilization of purine bases resulting to increased Uric acid

Lesch-Nyhan syndrome

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Toxemia of pregnancy and lactic acidosis
Ingestion of purine-rich diet
starvation

TIS

Hyperuricemia

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hyperuricemia
ingestion of purine rich diet

liver, kidney, shellfish, legumes

LKSL

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Secondary to liver disease
defective tubular reabsorption

hypouricemia

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disorder of reabsorption in the PCT

Fanconi’s Syndrome

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6-mercaptopurine or azathioprine
overtreatment with allopurinol

Chemotheraphy

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Based on the oxidation of UA in PFF with subsequent reduction of phospotungstic acid to tungsten blue

Caraway Method

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provides alkaline pH for color development

Sodium carbonate

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small collection of sodium urate crystals in the joint

Tophi

→ Has a MW of 168 Da

Filtered by the glomerulus

Exogenous

diet

Endogenous

liver, intestine and other tissues

Guanine will be acted upon by _________________

guanine deaminase

→ Guanosine will be converted to Guanine via ______________

nucleosidase

Guanine will be acted upon by _________________

guanine deaminase

Earlier uric acid crystal formation due to the abnormal levels of UA in the urine is demonstrated by the orange colored deposits in the diapers

Lesch Nyhan syndrome

Urate stones can also develop and is demonstrated by the blood in urine

Lesch Nyhan syndrome

Toxemia of pregnancy and lactic acidosis ▪ Ingestion of Purine-rich diet − Liver, kidney, shellfish, legumes ▪ Starvation; tissue catabolism induced by inadequate dietary intake

Hyperuricemia

− Competition with the rate of renal excretion because of the excess metabolites such as TAGs and lactate

▪ G6PD deficiency

− A disorder of reabsorption in the PCT

▪ Fanconi’s Syndrome:

▪ Secondary to liver disease ▪ Defective tubular reabsorption

→ Hypouricemia

− 6-mercaptopurine or azathioprine − Overtreatment with allopurinol

Chemotherapy

✓ Taken by RBCs and can decrease the formation of certain genetic material ✓ Inhibit purine synthesis ✓ Inhibits xanthine oxidase

Based on the oxidation of UA in PFF, with subsequent reduction of phosphotungstic acid to tungsten blue Lacks specificity

1. Caraway Method

Uricase catalyzes the oxidation of UA to allantoin → Measures the differential absorption of uric acid and allantoin at 293 nm → Uricase is also known as urate oxidase ● More specific ● Hemoglobin and xanthine can cause negative interference

2. Uricase Method

Uricase is also known as __________

urate oxidase

Uricase method → Measures the differential absorption of uric acid and allantoin at _______

293 nm

Lesch nyhan syndrome Earlier uric acid crystal formation due to the abnormal levels of UA in the urine is demonstrated by the __________ colored deposits in the diapers

color orange

Caraway method Due to the reaction above there will be formation of ________, _________ and__________

tungsten blue, allantoin, and carbon dioxide

Uricase method _______ and ________ can cause negative interference

Hemoglobin and xanthine

Measures the hydrogen peroxide produced as UA is converted to allantoin

Coupled Enzymatic Methods

catalyze a chemical indicator reaction

Peroxidase or catalase

medical term for kidney stones; composed of minerals and salts

Renal calculi

e is the appropriate term for the uric acid IN THE BLOOD

Monosodium urate

l if it is IN THE URINE

Uric acid crystal

uric acid crystals have a shape of ____________

rhombus shape

The remainder of uric acid is excreted into the GI tract __________

will be defecated

Transported by the plasma from the liver to the kidney, where it is filtered and where about 70% is excreted _________

Via urination

● Interference: bilirubin and ascorbic acid can destroy peroxide

Coupled enzymatic method Interference: __________ can destroy peroxide

bilirubin and ascorbic acid

increased blood cells

Polycythemia

Uric acid is oxidized to allantoin by ________

Enzymatic colorimetric

The generated hydrogen peroxide reacts with 4-aminophenazone/ESPT to quinoneimine

enzymatic colorimetric

→ DHBS stands for _____________

3,5 - dichloro-2-hydroxybenzenesulfonic acid

Within ___________ of liver failure, there is high probability that a person may die

30 minutes

ENZYMATIC COLORIMETRIC The generated hydrogen peroxide reacts with __________

4-aminophenazone / Ethyl-sulphopropyl toluidine (ESPT) to quinoneimine

Inhibits the action of the enzyme XANTHINE OXIDASE ➢ With this, xanthine will not be converted into uric acid, thus lowering uric acid concentration in the blood

Allopurinol

catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid ➢ responsible for the synthesis of uric acid

xanthine oxidase

Produced in the catabolism or deamination of amino acids and by bacterial metabolism in the lumen of the intestine

AMMONIA

Removed from the circulation and converted to urea in the liver

AMMONIA

is consumed by the parenchymal cells in the liver for the conversion of ammonia to ure

Ammonia

→ Ammonia can be secreted by the kidneys as _________and acts to buffer the urine

ammonium ions

▪ Fasting is not required − Diet can affect uric acid levels but recent meals have no effect ▪ Avoid lipemic and hemolyzed specimens ▪ May be refrigerated for 3-5 days

Serum

Falsely decreased results to peroxidase methods ✓ Addition of potassium ferricyanide and ascorbate oxidase

Ascorbic acid

---Salicylates → Thiazide

Drugs

In ascorbic acid there are addition of _____________

Addition of potassium ferricyanide and ascorbate oxidase PF and AO

In ascorbic acid there are addition of _____________

Addition of potassium ferricyanide and ascorbate oxidase PF and AO

→ Both can cause false increase

salicylates and thiazides

Disease Correlation

Hepatic failure ● Severe liver disease (most common cause of distrubed ammonia catabolism); increased ammonia level ● Inherited deficiency of urea cycle enzymes

● Complicated by its low concentration, instability, and pervasive contamination ● Glutamate dehydrogenase assay

Analytical methods

→ Causes swelling in the liver and brain → Often affects children and teenagers recovering from a viral infection, most commonly the flu or chickenpox

Reye’s Syndrome

ammonia concentration increases rapidly following specimen collection because of in vitro amino acid deamination

WHOLE BLOOD

Venous blood should be obtained ___________ and placed on ice immediately

WITHOUT TRAUMA

most preferred tube use in ammonia

Heparin (green tube)

Samples should be centrifuged at __________ within ______ minutes of collection and the plasma or serum removed * Hemolysis should be avoided

0 degrees to 4 degrees celcius at 20 minutes

In specimen requirement _______ should be avoided

hemolysis

Most common on automated instruments o Accurate and precise

Glutamate dehydrogenase assay

Give me the 2 chemical methods of analytic methods ammonia

1. ion-selective electrode 2. spectrophotometric

Give me 1 enzymatic methods of analytic method in ammonia

1. glutamate dehydrogenase