CC1 Lec - Bilirubin and Liver Biochemical Function

Liver

It is the only organ that is capable of processing and excreting bilirubin

Hemorrhage

People with liver disease may also develop?

Lipids

Major site for the removal of chylomicron remnants

Cell injury

Elevated levels of enzyme in the plasma indicates?

Small intestine

All substances absorbed from the ______ ___________ must first pass through the liver.

Cytochrome P-450

The drug-metabolizing system comprised of enzymes in the liver responsible for drug metabolism.

Bilirubin

• This is the end product of hemoglobin metabolism

• The principle pigment in bile

UDP-glucuronosyltransferase (UDPGT)

Which of the following enzymes is responsible for the conjugation of bilirubin?

Catalyzes the transfer of glucuronyl to each of the two propionic acid chains in bilirubin

Catalytic mechanism of UDPGT

Bilirubin diglucuronide (B2)

• Also known as the conjugated bilirubin

• Also known as Cholebilirubin

• Form of bilirubin that can be excreted as it is by the urine

Bile canaliculi

Excretion of B2 happens in the?

Hepatocytes

In which of the following types of cells does the conjugation of bilirubin take place?

Gall bladder

When bile is secreted from the liver, it is temporarily stored in the?

Bile

It emulsifies fats to promote fat digestion

Mesobilirubin

In the large intestine, bilirubin (B2) is processed by intestinal bacteria in order to become?

Mesobilirubinogen

Mesobilirubin in the intestine is further reduced to form?

Urobilinogen

• This compound is partially reabsorbed from the intestines through the portal circulation for reexcretion by the liver

• Mesobilirubinogen is further converted into this

• It is usually a colorless pigment

Urobilin / Stercobilin

Roughly 80% of urobilinogen is oxidized to become an orange-colored product known as?

Extrahepatic circulation

For the 20% remaining urobilinogen, they are reabsorbed in the?

Kidneys

The small quantity left of urobilinogen will now enter the systemic circulation and will subsequently filtered by the?

True

Extremely high bilirubin levels in the blood will allow bilirubin to be filtered / excreted as it is.

Bilirubin 1 (B1)

• Also known as unconjugated bilirubin

• Also known as Hemobilirubin

Delta albumin

• The bilirubin that is tightly bound to albumin

• It has a longer half-life than other forms of bilirubin

• It is formed due to prolonged elevation of conjugated bilirubin in biliary obstruction.

• It helps in monitoring the decline of serum bilirubin following surgical removal of gallstones

• It reacts with diazo reagent in the direct bilirubin assay

TB - DB + IB = Delta bilirubin

Formula for Delta bilirubin

Jaundice

Also called icterus or hyperbilirubinemia

Yellow discoloration of the skin, sclerae, and mucus membranes

Pre-hepatic bilirubinemia

Too much destruction of RBCs

Bilirubin assay: Elevated Indirect Bilirubin

Post-hepatic bilirubinemia

Failure of bile to flow to the intestine / impaired bilirubin excretion

Bilirubin assay: Elevated Direct Bilirubin

Hepatocellular Combine Hyperbilirubinemia

Hepatocyte injury caused by viruses, alcohol, and parasites

Bilirubin assay: Both Direct and Indirect Bilirubin are elevated

Gilbert’s Syndrome

• Associated with Bilirubin Transport Deficit

• Impaired cellular uptake of bilirubin

• Related to the enzyme UGT1A1

• Elevated B1

Crigler-Najjar Syndrome

• Inherited disorder of bilirubin metabolism resulting from a molecular defect with a gene involved in bilirubin conjugation

Phototherapy

In Crigler-Najjar Syndrome, infants are treated by means of?

Type I Crigler-Najjar Syndrome

• There is complete absence of enzymatic bilirubin conjugation

• Bile is colorless

Type II Crigler-Najjar Syndrome

There is mutation in the genes causing a severe deficiency of the enzyme responsible for conjugation.

Dubin Johnson Syndrome

• There is a deficiency in a protein transporter MDR2

• Bilirubin excretion deficit

• Blockade of the excretion of the bilirubin into the canaliculi

• Characterized by elevated total bilirubin and B2

• Elevations in conjugated bilirubin

Lucey Driscoll Syndrome

• Also known as the transient familial hyperbilirubinemia

• Rare condition wherein B1 and total bilirubin level of newborn are abnormally increased

• Familial form of unconjugated hyperbilirubinemia

Conjugated bilirubin

Which of the following fractions of bilirubin is water-soluble and reacts with a diazo reagent without the addition of an accelerator?

Azobilirubin

The product produced and measured when reacting bilirubin with a diazo reagent is?

Ammonia

Which of the following is measured using glutamate dehydrogenase and is a measure of advanced stages, poor prognosis, and coma in liver disease?

Biliary obstruction

In which of the following disease states would you see an elevation in total bilirubin and conjugated bilirubin only?

Intrahepatic ducts

The bile canaliculi are small spaces between the hepatocytes that form _____________, where excretory products of the cells can drain

Lobules

The liver is divided into microscopic units called

Kupffer cells

These are macrophages that line the sinusoids of the liver and act as active phagocytes capable of engulfing bacteria, debris, toxins, and other substances flowing through the sinusoids

Transamination

This results in the exchange of an amino group on one acid with a ketone group on another acid

Overt jaundice

Type of jaundice is usually not noticeable to the naked eye