Bilirubin Metabolism and Disorders

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which drug is known to cause isolated elevated bilirubin levels?

Isoniazid (correct)

Ibuprofen

Acetaminophen

Metformin

What is the predominant conjugated form of bilirubin?

Unconjugated bilirubin

Bilirubin sulfate

Bilirubin monoglucuronide

Bilirubin diglucuronide (correct)

What process converts bilirubin into urobilinogens in the intestine?

Bacterial metabolism (correct)

Hemolysis

Dehydration

Conjugation

What primarily prevents unconjugated bilirubin from binding to tissues?

Binding to albumin in plasma Signup and view all the answers

What is the main reason for elevated conjugated hyperbilirubinemia?

Interference with excretion Signup and view all the answers

Which condition is NOT a common cause of conjugated hyperbilirubinemia?

Dehydration Signup and view all the answers

What color changes would occur in the stool if urobilinogens are absent?

Clay color Signup and view all the answers

What is the primary source of bilirubin production in the body?

Degradation of hemoglobin Signup and view all the answers

Which condition is associated with an increased production of unconjugated bilirubin that can reach up to 70%?

Dyserythropoiesis disorders Signup and view all the answers

Which of the following can lead to decreased hepatic clearance of bilirubin?

Congestive heart failure Signup and view all the answers

Which drug is known to inhibit bilirubin uptake in the liver?

Rifampin Signup and view all the answers

What is the primary consequence of prolonged production of unconjugated bilirubin?

Formation of bilirubin salts and gallstones Signup and view all the answers

What is the primary treatment for type I Crigler-Najjar syndrome?

Emergent plasma exchange Signup and view all the answers

In patients with Crigler-Najjar syndrome type I, what can happen if left untreated?

Fatality by age two years Signup and view all the answers

Which of the following conditions is NOT associated with defective bilirubin conjugation?

Cirrhosis Signup and view all the answers

Which treatment may benefit patients with type II Crigler-Najjar syndrome?

Phenobarbital administration Signup and view all the answers

What is the normal range for total bilirubin in adults?

0.3-1.0 mg/dL Signup and view all the answers

Which condition is associated with unconjugated hyperbilirubinemia?

Increased red blood cell destruction Signup and view all the answers

What bilirubin level is considered critical for adults?

<blockquote> 12 mg/dL </blockquote> Signup and view all the answers

What age group commonly exhibits unconjugated hyperbilirubinemia due to hematocrit levels?

Newborns Signup and view all the answers

What is one mechanism that can cause increased production of unconjugated bilirubin?

Hemolysis of red blood cells Signup and view all the answers

Which of the following diseases is relatively rare except in specific populations?

Dubin-Johnson syndrome Signup and view all the answers

What is the average lifespan of a red blood cell in a newborn?

85 days Signup and view all the answers

Conjugated hyperbilirubinemia is commonly linked to which of the following?

Sepsis Signup and view all the answers

Study Notes

Increased Bilirubin Production

Dyserythropoiesis can lead to an increase in unconjugated bilirubin production, reaching up to 70% in cases of thalassemia major, megaloblastic anemia, congenital erythropoietic porphyria, and lead poisoning.
Prolonged production of unconjugated bilirubin can lead to bilirubin salt precipitation and subsequent gallstone formation.

Decreased Hepatic Clearance

Congestive heart failure, cirrhosis/portosystemic shunts, and certain drugs can cause decreased hepatic clearance of bilirubin.
Congestive heart failure or portosystemic shunts can impair bilirubin delivery to the liver, reducing hepatic uptake.
Cirrhosis can result in unconjugated hyperbilirubinemia due to capillarization of sinusoids, affecting bilirubin uptake by hepatocytes.
Drugs like rifamycin, rifampin, probenecid, flavaspidic acid, and bunamiodyl can inhibit bilirubin uptake, but this effect is reversible upon cessation of these medications.

Defective Bilirubin Conjugation

Inherited conditions like Crigler-Najjar syndrome types I and II, and Gilbert syndrome are associated with defective bilirubin conjugation.
Ethinyl estradiol and hyperthyroidism can also contribute to defective conjugation.
Crigler-Najjar syndrome, a rare autosomal-recessive disorder, involves an alteration in the bilirubin-UGT gene responsible for bilirubin conjugation.
Type I Crigler-Najjar syndrome results in a complete or near-complete loss of UGT function, while Type II presents with low UGT activity.
Type I Crigler-Najjar syndrome typically presents with high unconjugated bilirubin levels at birth, leading to kernicterus. Treatment involves plasma exchange and phototherapy.
Type II Crigler-Najjar syndrome may not require treatment or can be managed with phenobarbital, which induces UGT expression.
Type I Crigler-Najjar syndrome does not respond to phenobarbital due to the loss-of-function mutation.

Other Causes of Conjugated Hyperbilirubinemia

Drugs like isoniazid, chlorpromazine, erythromycin, and anabolic steroids can cause conjugated hyperbilirubinemia.
Sepsis, shock, and hemochromatosis are also associated with conjugated hyperbilirubinemia.

Bilirubin Testing

Plasma (heparin) or serum samples are used for bilirubin testing.
Bilirubin is a breakdown product of heme, primarily derived from hemoglobin degradation.
Unconjugated bilirubin is water-insoluble and binds to albumin in the plasma.
Hepatocytes take up unconjugated bilirubin and conjugate it via uridine diphosphoglucuronate glucuronosyltransferase (UGT), creating a water-soluble form.
Conjugated bilirubin is excreted into bile and delivered to the small intestine.
Intestinal bacteria convert bilirubin into urobilinogens.
Urobilinogens are reabsorbed and circulated back to the liver (enterohepatic circulation) or excreted in urine and stool.
Elevated Total Bilirubin levels (>2.5-3 mg/dL) indicate jaundice and can be classified into prehepatic, hepatic, or posthepatic causes.
Unconjugated hyperbilirubinemia is common in newborns due to high hematocrit and decreased UGT activity.

Common causes of Unconjugated and Conjugated Hyperbilirubinemia

Unconjugated hyperbilirubinemia:*
Increased bilirubin production from hemolysis and dyserythropoiesis: Hemolysis leads to increased red blood cell destruction and bilirubin production.
Conjugated hyperbilirubinemia:*
Hepatocellular injuries: Conditions affecting liver cells can lead to impaired conjugation and bile excretion.
Biliary obstruction: Obstruction of bile ducts can prevent bilirubin flow to the intestines.

Normal bilirubin values:

Adults/elderly/children: Total bilirubin: 0.3 - 1.0 mg/dL or 5.1 - 17 μmol/L (SI units); Indirect bilirubin: 0.2 - 0.8 mg/dL or 3.4 - 12.0 μmol/L (SI units); Direct bilirubin: 0.1 - 0.3 mg/dL or 1.7 - 5.1 μmol/L (SI units).
Newborns: Total bilirubin: 1.0 - 12.0 mg/dL or 17.1 - 205 μmol/L (SI units)

Possible critical values:

Adults: Total Bilirubin > 12 mg/dL
Newborns: Total Bilirubin > 15 mg/dL

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the mechanisms behind increased bilirubin production and decreased hepatic clearance. This quiz delves into conditions such as dyserythropoiesis, cirrhosis, and factors influencing bilirubin metabolism.