Hemoglobin Structure and Function Quiz

Hemoglobin Structure and Synthesis

• Hemoglobin is an iron-containing protein found in red blood cells, responsible for oxygen transport.
• Hemoglobin synthesis begins in the proerythroblast and continues until the reticulocyte stage.
• Hemoglobin synthesis involves the formation of a porphyrin ring, which binds to iron to form heme.
• Four polypeptide chains, two alpha and two beta, combine with heme to form a hemoglobin molecule.

Hemoglobin Abnormalities

• Abnormal hemoglobin arises from gene mutations, often affecting the polypeptide chain.
• Sickle cell hemoglobin (Hb S) is a common example.
• Sickle cell hemoglobin arises from a substitution of valine for glutamate in the beta chain at position 6.
• Hb S has lower oxygen affinity and polymerizes under low oxygen tension, leading to red blood cell sickling, aggregation, and ischemia.

Factors Affecting Oxygen Binding to Hemoglobin

• The affinity of hemoglobin for oxygen is affected by various factors.
• The type of polypeptide chain determines oxygen affinity, with Hb F having higher affinity than Hb A.
• Carbon dioxide, hydrogen ions, temperature, and 2,3-diphosphoglycerate (2,3-DPG) concentration affect oxygen affinity.
• Increased carbon dioxide, hydrogen ions, temperature, and 2,3-DPG decrease oxygen affinity.

Carbaminohemoglobin

• Hemoglobin reversibly binds to carbon dioxide at the amino terminal of the polypeptide chain.
• Carbaminohemoglobin carries approximately 5% of carbon dioxide in the blood.

Methaemoglobin and Carboxyhemoglobin

• Methaemoglobin (Met Hb) is formed when the ferrous ion (Fe2+) in heme is oxidized to ferric ion (Fe3+) by oxidizing agents, preventing oxygen binding.
• Carboxyhemoglobin (Carboxy Hb) arises when carbon monoxide (CO) binds to hemoglobin.
• Carbon monoxide has a much higher affinity for hemoglobin than oxygen, displacing oxygen and rendering hemoglobin unable to carry oxygen.

Hemoglobin Breakdown and Bilirubin Formation

• When red blood cells are destroyed, hemoglobin is broken down.
• The polypeptide portion of hemoglobin is hydrolyzed into amino acids and released into circulation.
• Iron is removed from heme and released back into the plasma bound to transferrin.
• The porphyrin ring is converted to biliverdin, and subsequently to bilirubin.

Bilirubin Metabolism

• Unconjugated bilirubin is insoluble in water and binds to albumin in the plasma.
• In the liver, bilirubin conjugates with glucouronic acid, becoming water-soluble.
• Conjugated bilirubin is secreted into bile and excreted in feces.
• Conjugated bilirubin in bile is converted into stercobilinogen and urobilinogen by intestinal bacteria.
• Stercobilinogen provides the brown color to feces.
• Urobilinogen is colorless and partially reabsorbed into the portal blood.
• Most reabsorbed urobilinogen is re-excreted in bile, while a small percentage is secreted in urine.

Jaundice

• Jaundice refers to a yellow discoloration of the skin, sclera, and mucous membranes, caused by increased bilirubin levels in the blood.
• Jaundice can be classified into three types based on the cause: hemolytic, hepatic, and obstructive jaundice.

Hemolytic Jaundice

• Increased red blood cell destruction leads to increased levels of unconjugated bilirubin in the blood, which cannot be secreted in the urine.
• The liver conjugates and excretes bilirubin at a higher rate.
• Increased production of urobilinogen results in elevated urinary urobilinogen levels.

Hepatic Jaundice

• Liver dysfunction prevents conjugation of bilirubin, causing elevated unconjugated bilirubin levels in the blood and no bilirubin secretion in urine.
• Failure to secrete conjugated bilirubin into bile leads to increased conjugated bilirubin in the blood and urine.
• Conjugated bilirubin predominates in hepatocellular liver disease due to impaired biliary secretion caused by cell injury.

Obstructive Jaundice

• An obstruction to bile flow, such as a tumor or gallstone, prevents secreted conjugated bilirubin from reaching the intestines.
• Conjugated bilirubin leaks back into the bloodstream, resulting in high conjugated bilirubin levels in the blood and urine.
• Bile obstruction leads to pale stools due to absent stercobilinogen, fat malabsorption, and vitamin K deficiency.
• No urobilinogen is detected in urine.

Physiological Hyperbilirubinemia and Jaundice

• During fetal life, bilirubin crosses the placenta and is excreted by the mother's liver.
• The fetus's liver has limited bilirubin conjugation capacity in the first few days after birth.
• Mild unconjugated bilirubin accumulation occurs in newborns, which is usually transient.