2. Chapter 3. waste products

What are waste products?

Substances produced by metabolism that are no longer useful and can be harmful if they accumulate.

Which waste products are important in clinical biochemistry?

Bilirubin, urea, creatinine, and uric acid.

What is bilirubin?

A waste product formed during heme metabolism.

Most bilirubin comes from what?

Breakdown of hemoglobin from old red blood cells.

Which molecules contain heme?

Hemoglobin, myoglobin, cytochromes, catalase, and peroxidase.

What is the first step of bilirubin formation?

Heme is converted to biliverdin by heme oxygenase.

What color is biliverdin?

Green.

What is biliverdin converted into?

Bilirubin.

Which enzyme converts biliverdin into bilirubin?

Biliverdin reductase.

What color is bilirubin?

Yellow.

What is unconjugated bilirubin?

Water-insoluble bilirubin bound to albumin in blood.

Why does unconjugated bilirubin bind albumin?

Because it is water-insoluble and cannot circulate freely.

Where is unconjugated bilirubin conjugated?

In the liver.

What is bilirubin conjugated with?

Glucuronic acid.

Why is bilirubin conjugated?

To make it water-soluble for excretion in bile.

Where does conjugated bilirubin go after the liver?

Into bile and then into the intestine.

What do gut bacteria convert bilirubin into?

Urobilinogen.

What gives stool its brown color?

Stercobilin.

What gives urine its yellow color?

Urobilin.

Is bilirubin normally present in healthy urine?

No.

What is jaundice?

Yellow discoloration of skin and sclera caused by increased bilirubin.

What is hyperbilirubinemia?

Increased bilirubin concentration in blood.

What are the three main types of jaundice?

Prehepatic, hepatic, and posthepatic jaundice.

What is prehepatic jaundice?

Jaundice caused by excessive bilirubin production before the liver.

What is the common cause of prehepatic jaundice?

Hemolysis.

Which bilirubin is mainly increased in prehepatic jaundice?

Unconjugated bilirubin.

Is bilirubin present in urine in prehepatic jaundice?

No.

Why is bilirubin absent in urine in prehepatic jaundice?

Unconjugated bilirubin is albumin-bound and water-insoluble.

What happens to urobilinogen in prehepatic jaundice?

It is increased.

What happens to stool color in prehepatic jaundice?

It becomes darker due to increased stercobilin.

What is hepatic jaundice?

Jaundice caused by liver cell damage.

Which diseases can cause hepatic jaundice?

Hepatitis, cirrhosis, and liver cancer.

Which bilirubin types increase in hepatic jaundice?

Both unconjugated and conjugated bilirubin can increase.

Why does bilirubin increase in hepatic jaundice?

Damaged hepatocytes cannot properly uptake, conjugate, or excrete bilirubin.

What happens to ALT and AST in hepatic jaundice?

They are usually increased.

What is posthepatic jaundice?

Jaundice caused by obstruction after the liver.

Common causes of posthepatic jaundice

Gallstones or tumors blocking bile ducts.

Which bilirubin is mainly increased in posthepatic jaundice?

Conjugated bilirubin.

Why is urine dark in posthepatic jaundice?

Conjugated bilirubin is water-soluble and enters urine.

Why is stool pale in posthepatic jaundice?

Bilirubin cannot reach the intestine, so stercobilin is reduced.

What happens to urobilinogen in posthepatic jaundice?

It is decreased or absent.

Which enzyme is strongly increased in obstructive jaundice?

ALP.

Prehepatic jaundice pattern

Unconjugated bilirubin increased, urine bilirubin absent, urobilinogen increased, stool dark.

Hepatic jaundice pattern

Mixed increase of unconjugated and conjugated bilirubin, ALT and AST increased.

Posthepatic jaundice pattern

Conjugated bilirubin increased, dark urine, pale stool, urobilinogen decreased, ALP highly increased.

What is Gilbert syndrome?

Benign condition with mild unconjugated hyperbilirubinemia.

Are liver function tests normal in Gilbert syndrome?

Yes.

Is bilirubin present in urine in Gilbert syndrome?

No.

What is Crigler-Najjar syndrome type 1?

Complete absence of UDP-glucuronyl transferase.

Which bilirubin is very high in Crigler-Najjar type 1?

Unconjugated bilirubin.

Why is Crigler-Najjar type 1 dangerous?

Very high unconjugated bilirubin can cause kernicterus.

What is the treatment for Crigler-Najjar type 1?

Early liver transplantation.

What is Crigler-Najjar syndrome type 2?

Partial deficiency of UDP-glucuronyl transferase.

Which therapy helps in Crigler-Najjar type 2?

Phenobarbital.

What are Dubin-Johnson and Rotor syndromes?

Benign disorders with conjugated hyperbilirubinemia.

What is characteristic for Dubin-Johnson syndrome?

Black liver pigmentation.

What is physiological jaundice of newborns?

Common harmless unconjugated hyperbilirubinemia appearing after birth.

When does physiological newborn jaundice usually appear?

Between the 2nd and 5th day of life.

Why do newborns get physiological jaundice?

Short RBC lifespan and immature bilirubin conjugation.

Why is unconjugated bilirubin dangerous in newborns?

It is lipid-soluble and can cross the blood-brain barrier.

What is kernicterus?

Brain damage caused by very high unconjugated bilirubin.

What is conjugated hyperbilirubinemia in newborns caused by?

Neonatal hepatitis or biliary atresia.

What is biliary atresia?

Defect of bile ducts causing bile accumulation in the liver.

Treatment of biliary atresia

Surgical treatment.

Most common bilirubin measurement method

Diazo method.

Principle of the diazo method

Bilirubin reacts with diazo reagent to form colored azobilirubin.

What does diazo method without accelerator measure?

Direct conjugated bilirubin.

What does diazo method with accelerator measure?

Total bilirubin.

How is urine bilirubin usually detected?

Test strips.

What color indicates positive urine bilirubin on test strips?

Pink coloration.

What is urea?

Waste product of protein metabolism.

Where is urea formed?

In the liver.

Why is urea formed?

To convert toxic ammonia into a safer molecule.

Which cycle forms urea?

Urea cycle.

Where is urea excreted?

Mainly by the kidneys in urine.

How much urea is excreted in urine?

More than 90%.

What is BUN?

Blood urea nitrogen, the nitrogen part of urea in blood.

Formula for urea from BUN

Urea = 2.14 × BUN.

Formula for BUN from urea

BUN = 0.466 × urea.

What is uremia?

Serum urea concentration above reference value.

Why does urea increase in kidney dysfunction?

The kidneys cannot excrete urea properly.

Extra-renal causes of increased urea

High-protein diet, dehydration, protein breakdown, postrenal obstruction, heart disease, cortisol treatment.

Why is urea not a perfect kidney marker?

It is affected by diet, hydration, liver function, and protein metabolism.

What causes decreased urea?

Malnutrition and severe liver disease.

Why does liver disease decrease urea?

The liver cannot synthesize urea properly.

How is urea measured?

By enzymatic breakdown with urease and measuring produced ammonia.

Which enzyme breaks down urea in lab tests?

Urease.

What products are formed from urea by urease?

Ammonia and carbon dioxide.

Which urea method is common in automated analyzers?

Kinetic photometric method using glutamate dehydrogenase.

What is creatinine?

Waste product formed from creatine and phosphocreatine.

Where is creatinine mainly produced?

Skeletal muscle.

Creatinine formation depends mainly on what?

Muscle mass.

How is creatinine eliminated?

Through the kidneys.

How is creatinine handled by the kidney?

Freely filtered, minimally reabsorbed, and slightly secreted.

Why is creatinine useful for kidney function?

It is produced relatively constantly and filtered by the glomeruli.

What are the two main factors affecting serum creatinine?

Muscle mass and kidney function.

What happens to creatinine in reduced kidney function?

It increases.

Why can creatinine miss early kidney disease?

It may rise clearly only in more advanced kidney dysfunction.

What is GFR?

Glomerular filtration rate, showing how well kidneys filter blood.

What GFR suggests kidney disease?

Below 60 ml/min/1.73 m².