Destruction of Red Blood Cells

Introduction

• The average lifespan of red cells is about 120 days.
• Aging cells become less flexible and more rigid.
• These cells are trapped in the spleen and liver by macrophages.
• Macrophages remove them through phagocytosis.
• Hemoglobin is released and broken down for reuse.
• Some rigid cells may rupture while passing through narrow capillaries.

Mechanisms Of Destruction

• Red cell destruction occurs by intravascular and extravascular mechanisms

Intravascular Destruction

• In intravascular hemolysis, red cells rupture within the circulation.
• It occurs when the membrane integrity is compromised.
• Aging increases membrane rigidity and susceptibility to rupture.
• Membrane defects enhance vulnerability to mechanical stress.
• Complement-mediated injury produces membrane pores and lysis.
• It is seen in microangiopathic hemolytic anemia and prosthetic valve–related hemolysis.
• Free hemoglobin is released directly into plasma.

Extravascular Destruction

• In extravascular hemolysis, macrophages remove red cells in spleen, liver, and bone marrow.
• Senescent cells are recognized and phagocytosed.
• Two major factors promote this process: decreased deformability and altered surface properties.

Decreased Deformability

• Normal deformability allows passage through narrow capillaries and splenic sinusoids.
• Loss of flexibility leads to trapping and destruction in the spleen.
• Shape abnormalities such as spherocytosis and elliptocytosis reduce deformability.
• Increased intracellular viscosity, as in sickling disorders, also impairs flexibility.

Alteration in Surface Properties

• Binding of antibodies or complement changes membrane composition.
• These changes mark cells for recognition by macrophages.
• Immunoglobulin or complement deposition enhances phagocytosis.
• Oxidative damage to membrane components further promotes destruction.

Fate Of Destroyed Red Cells

• Destruction of red cells releases hemoglobin, which is split into heme and globin.
• Globin is degraded into amino acids and reused.
• Heme is converted into bile pigments, mainly bilirubin.

Fate in Intravascular Destruction

• Hemolysis in circulation releases free hemoglobin into plasma.
• Hemoglobin binds to haptoglobin, forming a complex transported to the liver.
• In the liver, heme is broken down into iron and biliverdin by heme oxygenase.
• Carbon monoxide is released during this process.
• Biliverdin is converted to bilirubin.
• Free heme binds to hemopexin for transport.
• When binding capacity is exceeded, heme associates with albumin as methemalbumin.

Fate in Extravascular Destruction

• In extravascular hemolysis, macrophages degrade red cells within spleen and liver.
• Hemoglobin is broken into heme, proteins, and lipids.
• Heme is converted to bilirubin, while proteins and lipids are reutilized.
• Bilirubin is transported to the liver and excreted in bile.
• In the intestine, it is converted to urobilinogen by bacteria.
• Urobilinogen is further converted to stercobilin and excreted in stool.
• A small amount is reabsorbed and excreted in urine as urobilinogen.

Hemolytic Jaundice

• Hemolytic jaundice results from increased destruction of red cells, leading to excess bilirubin formation.
• The liver can normally handle increased bilirubin load, so jaundice is often mild in adults.
• In newborns, immature liver enzymes reduce conjugation, making jaundice more common.
• Heme is converted to biliverdin and then to bilirubin.
• Unconjugated bilirubin binds to albumin and is transported to the liver.
• In hepatocytes, it is conjugated to bilirubin diglucuronide.
• Conjugated bilirubin is excreted in bile into the intestine.
• Intestinal bacteria convert it to urobilinogen.
• Some urobilinogen is reabsorbed and excreted in urine.
• Most is converted to stercobilin and excreted in stool.
• Increased stercobilin causes dark-colored stools.
• Urinary urobilinogen is elevated in hemolysis.
• Unconjugated bilirubin is not excreted in urine, so urine remains free of bilirubin.
• Hence, this condition is termed acholuric jaundice.
• Plasma bilirubin is moderately elevated, usually below 6 milligrams per deciliter.
• Liver function tests are generally normal.

Table 13.1: Causes of hemolytic jaundice

Category	Major Causes
Inherited disorders	Membrane defects (spherocytosis, elliptocytosis), enzyme deficiencies (glucose-6-phosphate dehydrogenase, pyruvate kinase), hemoglobinopathies such as sickle cell disease
Acquired disorders	Microangiopathic hemolysis, paroxysmal nocturnal hemoglobinuria, immune-mediated hemolysis, incompatible transfusion, drug-induced hemolysis, severe burns