Urinalysis-metabolic disorders

What is an overflow disorder?

Disruptions of a normal metabolic pathway that causes increased plasma concentrations of the non-metabolized substances

What is a renal type disorder?

Caused by malfunctions in the tubular reabsorption mechanism

What is an inborn error of metablosim?

Disruption of enzyme function caused by failure to inherit the gene to produce a particular enzyme

What pathway is interrupted in phenylketonuria (PKU)?

Conversion of phenylalanine to tyrosine

What three disorders are IMB of the melanin pathway?

• phenylketonuria

• tyrosinemia

• alkaptonuria

What enzyme is missing in phenylektonuira?

phenylalanine hydroxylase

What are the follow-up tests used to detect pku in urine?

• Benedict test

• ferric chloride test which turns the urine blue-green if phenylpyruvic acid is present

• silver nitrate test

What is tyrosyluria cause by?

• underdevelopment of the liver

• severe liver disease

What abnormal crystals are seen in tyrosyluria?

Tyrosine and leucine

How is tyrosyluria type 1 detected?

Increase in tyrosine and succinylacetone in the blood and urine

What enzyme is missing in type one tyrosinemia?

fumarylacetoacetate hydrolase

What enzyme is missing in type 2 tyrosinemia?

tyrosine aminotransferase

What enzyme is missing in type 3 tyrosinemia?

p-hydroxyphenylpyrivic acid dioxygenase

What is melanuria?

Increase of melanin in the urine, darkening the urine and usually associated with malignant melanoma

What is alkaptonuria?

Accumulation of homogentisic acid in the urine, turning urine brown/black

What is maple syrup disease?

A IEM caused by the failure to inherit the enzyme for oxidative decarboxylation of leucine, isoleucine and valine. Causing keto acid to accumulate in the urine

What are the three organic acidemias?

• isovaleric

• propioinc

• methylmalonic

What odor is present in isovaleric?

sweaty feet caused by the accumulation of isovalerylglycine

What is indicanuria?

Increased amounts of tryptophan are converted to indole where it circultes in the bloodstream until it is converted to indican by the liver

What happens to indican when exposed to the air?

turns blue

What is the nitroso-naphthol test for tyrosine?

Urine is mixed with nitric acid, sodium nitrite and -nitroso-2-napthol. An orange-red color changes indicated tyrosine metabolites

Where does homogentisic acid start to accumulate in alkaptonuria?

Body tissues, blood and urine

What color does the ferric chloride test turn when homogentisic acid is present?

Deep blue

What can be seen when homogentisic acid is present when performing the clintest?

Yellow precipitate (Reducing substance)

What are the two major groups of branched-amino acid disorders?

• maple syrup disease

• organic acidemias

What test is used to screen for MSUD?

2,4-DNPH. Urine and 2,4-DNPH are added to a tube and observed for a yellow turbidity or precipitate

What are the two tryptophan disorders?

• indicanuria

• 5-hydroxyindoleacetic acid

What causes indicanuria?

Intestinal disorders (obstruction, abnormal bacteria, malabsorption disorders and hartnup disease), causes spillover as increased amounts of tryptophan are converted to indole

When does urine turn blue in indicanuria?

When exposed to the air

What do increased amounts of 5-hydroxyindoleacetic acid in the urine usually signify?

Carcinoid tumors, 5-HIAA is a degradation product of serotonin and only appears in small amounts in the urine. Increased amounts indicate tumors producing serotonin in excess

What test is used to detect 5-HIAA?

Silver nitroprusside. Silver nitrate and NH4OH along with Silver nitroprusside are added to urine and observed for a purple-blank color change

What are the two disorders of cystine metabolism?

• cystinuria

• cystinosis

What is cystinuria?

Increased cystine in the urine due to the inability of renal tubules to reabsorb cystine

What are the two modes of inheritance with cystinuria?

• one where cystine, lysine, arginine and ornithine are not absorbed

• one where only cystine and lysine are not absorbed

What is cystinosis?

A genuine IEM where defects in the lysosomal membranes prevents the release of cystine into the cellular cytoplasm for metabolism, leading to accumulation

What can cystinosis lead to?

Organ damage and renal failure due to cystine deposits in the renal tubules

What is the cyanide nitroprusside test for cystine?

Urine and sodium cyanide are mixed, sodium nitroprusside is then added and observed for a red-purple color.

What is homocystinuria the result of?

Defects in the metabolism of methionine leading to an increase of homocystinuria in the body

How do we test for homocystinuria?

Following a positive cyanide-nitroprusside test a silver nitroprusside test is performed and observed for a red-purple color.

What are porphyrin disorders?

Problems with the breakdown and/or synthesis of hemoglobin

Which porphyrins readily appear in urine?

• ALA

• porphobilinogen

• uroporphyrin

Which porphyrin compounds are not readily seen in urine?

• Coproporphyrin (found in urine but not very soluble)

• protoporphyrin (not seen at all)

  Fecal analysis usually used to detect both these compounds

What are some common caused of porphyrias?

• lead poisoning

• excessive alcohol intake

• iron deficiency

• chronic liver disease

• renal disease

What is a possible indication of porphyrinuria?

Port-wine colored urine upon exposure to the air

What can Ehrlich reaction be used to detect?

ALA and porphobilinogen

In the watson-schwartz test what results are seen with urobilinogen?

Urobilinogen is soluble in both chloroform and butanol so both those layers will be red

In the watson-schwartz test what results are seen with porphobilinogen?

Porphobilinogen is insoluble in both chloroform and butanol so red color will remain in the urine layers

In the watson-schwartz test what results are seen with other ehrlich reactive copounds?

Soluble in butanol and insoluble in chloroform

If both layers of the watson-schwartz test are red what is present?

Both urobilinogen and porphobilinogen

What is the Hoesch screening test?

Urine is added to Hoesch reagent (Ehrlich reagent in HCl) and observed for a red color seen throughout the tube when shaken