Red blood cell destruction and Bilirubin

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Questions and Answers

What is the definition of Haematopoiesis?

The formation of blood cells.

What are the three sites of blood cell formation during Haematopoiesis?

Yolk sac, Lungs, Heart

Thymus, Spleen, Bone Marrow

Brain, Liver, Spleen

Yolk sac, Liver, Bone marrow (correct)

During which period does Haematopoiesis occur in the yolk sac?

Mesoblastic period (2 months)

What is the name for the clusters of mesodermal cells in the embryonic yolk sac where Haematopoiesis occurs in the mesoblastic period?

Blood islands Signup and view all the answers

Which organ becomes the major site of Haematopoiesis during the hepatic period?

Liver Signup and view all the answers

What is the name for the period of haematopoiesis when the bone marrow becomes the major site of blood cell production?

Myeloid phase Signup and view all the answers

The thymus gland is an important site for the production of lymphocytes and monocytes during the hepatic period.

False Signup and view all the answers

During the first five years of life, myeloid Haematopoiesis occurs practically in all bone marrow.

True Signup and view all the answers

What is the name for the process of blood cell formation that occurs outside the bone marrow, in tissues like the liver and spleen, in certain disease conditions?

Extramedullary Haematopoiesis Signup and view all the answers

What is the name for the pluripotent stem cell found in bone marrow that is a precursor to all blood cells?

Hemocystoblast Signup and view all the answers

The uncommitted bone marrow pluripotent stem cell is considered ______.

multipotential Signup and view all the answers

Which of the following cytokine(s) are involved in the differentiation of the uncommitted bone marrow pluripotent stem cell into committed bone marrow stem cells?

FLT3 Signup and view all the answers

Which of the following cytokines are involved in the differentiation of the uncommitted bone marrow pluripotent stem cell into committed lymphocyte stem cells?

IL-12 Signup and view all the answers

What specific type of progenitor cell is responsible for producing B and T cells?

Common lymphoid progenitor Signup and view all the answers

Match the following progenitor cells with their corresponding lineage:

Erythrocyte stem cell = Red blood cell Neutrophil/Monocyte stem cell = Neutrophils and monocytes Basophil stem cell = Basophils Eosinophil stem cell = Eosinophils Megakaryocyte stem cell = Platelets Signup and view all the answers

What is the name for the earliest discernible mature form of a particular blood cell that is still actively mitotic?

Blast cell Signup and view all the answers

Blast cells are the mature, non-dividing forms seen in circulation.

False Signup and view all the answers

Which of the following are characteristics of the differentiation of a blast cell into a mature blood cell?

Decrease in mitosis Signup and view all the answers

What is the function of the SCF cytokine?

Stem cell factor Signup and view all the answers

What is the scientific consensus regarding the origin of all blood cells?

All blood cells are believed to originate from a pluripotent or multipotent stem cell, also known as a hemocystoblast. Signup and view all the answers

The hemocystoblast actively differentiates into committed stem cells when stimulated by specific hormones or ligands.

True Signup and view all the answers

Committed stem cells are capable of dividing indefinitely and can give rise to all types of blood cells.

False Signup and view all the answers

The lifespan of red blood cells is measured by observing the disappearance of a tracer substance, known as a 'label,' from the bloodstream.

True Signup and view all the answers

Which tracer substance is frequently used for measuring red blood cell lifespan?

Radioactive Chromium Signup and view all the answers

How long is the average lifespan of red blood cells in human circulation?

Approximately 120 days Signup and view all the answers

What is the process by which senescent red blood cells are removed from circulation?

Phagocytosis by macrophages Signup and view all the answers

Which of the following are sites where phagocytosis of senescent red blood cells mainly occurs?

Spleen Signup and view all the answers

Macrophages can recognize and engulf only red blood cells, as they are unable to distinguish them from other types of cells.

False Signup and view all the answers

Which of the following are senescence markers that macrophages recognize on worn-out red blood cells?

Decreased surface area Signup and view all the answers

What happens to the components of a red blood cell after it's phagocytosed?

They are reutilized. Signup and view all the answers

The aging process of red blood cells is characterized by a decrease in both metabolic and structural alterations, resulting in an overall increase in cell function.

False Signup and view all the answers

The decrease in metabolic activity of red blood cells is primarily due to the loss of specific enzymes, such as aspartate aminotransferase and esterase.

True Signup and view all the answers

The accumulation of oxidative stress within red blood cells is a natural process that doesn't contribute to their aging and eventual removal.

False Signup and view all the answers

The relative contribution of senescence signals to the phagocytosis of red blood cells is well-understood and fully characterized.

False Signup and view all the answers

What percentage of red blood cell phagocytosis occurs intravascularly?

Approximately 10-20% Signup and view all the answers

What percentage of red blood cell phagocytosis is attributed to macrophages?

Approximately 80% Signup and view all the answers

Which of the following are tissues where macrophages are found and play a significant role in phagocytosing red blood cells?

Brain Signup and view all the answers

The term 'reticuloendothelial system' was originally coined to encompass all macrophages in the body, based on their shared origin from monocytes.

True Signup and view all the answers

The current understanding of the monocyte-macrophage system (MMS) now recognizes the separate origins and functions of macrophages throughout the body.

True Signup and view all the answers

What happens to the haemoglobin molecule when a red blood cell is phagocytosed by a macrophage?

Haemoglobin is separated from the heme and is broken down into amino acids. Signup and view all the answers

What is the purpose of the heme molecule being oxidized by the enzyme microsomal haem oxygenase?

To break down the tetrapyrrole ring structure of heme and produce biliverdin and iron. Signup and view all the answers

Biliverdin is a straight-chain molecule while bilirubin is a cyclic molecule.

False Signup and view all the answers

Where is iron stored in macrophages, making it available for the synthesis of new heme?

Ferritin Signup and view all the answers

What enzyme converts biliverdin to bilirubin?

Biliverdin reductase Signup and view all the answers

Increased serum bilirubin levels in adults are typically associated with a significant increase in red blood cell destruction.

False Signup and view all the answers

Elevated serum bilirubin levels in newborns are always indicative of a significant increase in red blood cell destruction.

False Signup and view all the answers

What condition can arise in newborns with excessive serum bilirubin levels?

Kernicterus Signup and view all the answers

Treatment options for kernicterus in newborns include blue light therapy and synthetic porphyrins that contain tin or zinc instead of iron.

True Signup and view all the answers

Bilirubin is a water-soluble molecule and is transported in the blood free from albumin.

False Signup and view all the answers

What is the upper limit of normal bilirubin concentration in the blood?

1.5 mg/dL Signup and view all the answers

What condition arises when the bilirubin concentration in the blood exceeds 2 mg/dL?

Jaundice Signup and view all the answers

Bilirubin is removed from the blood primarily by the kidneys.

False Signup and view all the answers

The uptake of bilirubin by hepatocytes in the liver involves the breakdown of the albumin-bilirubin bond, with albumin remaining in the plasma.

True Signup and view all the answers

What happens when bilirubin is not conjugated in the liver?

Unconjugated hyperbilirubinemia occurs. Signup and view all the answers

Gilbert's disease is a liver disorder that is often caused by a deficiency in the uptake of bilirubin by hepatocytes.

True Signup and view all the answers

The conjugation of bilirubin in the liver involves the binding of bilirubin to cytoplasmic proteins, such as ligands and 2-proteins.

True Signup and view all the answers

What is the main function of ligands and 2-proteins in the liver?

To bind to fatty acids and prevent the reflux of free bilirubin back into the bloodstream. Signup and view all the answers

The conjugation of bilirubin is a quick process, occurring within minutes.

False Signup and view all the answers

What is the primary mechanism by which cells neutralize unwanted compounds?

Conjugating them with a modified sugar, a process known as glycosylation. Signup and view all the answers

The conjugation of bilirubin involves the addition of xylose, glucose, or glucuronic acid to bilirubin, rendering it more hydrophilic and easier to excrete.

True Signup and view all the answers

The enzyme uridine diphosphate glucuronosyl transferase, or UDP-glucuronosyl transferase, catalyzes the conjugation of bilirubin with glucuronic acid.

True Signup and view all the answers

What is the condition where unconjugated bilirubin accumulates in the blood due to a deficiency in the enzyme responsible for conjugating it?

Crigler-Najjar syndrome Signup and view all the answers

The excretion of conjugated bilirubin involves the active transport of conjugated bilirubin from the liver into the bile canaliculi, forming the bile duct.

True Signup and view all the answers

In Dubin-Johnson syndrome, the accumulation of conjugated bilirubin in the liver is caused by a deficiency in the excretion of conjugated bilirubin into bile.

True Signup and view all the answers

What is the name for the process by which bilirubin is reabsorbed in the small intestine, transported back to the liver, and re-excreted without further conjugation?

Enterohepatic circulation Signup and view all the answers

The breakdown of bilirubin diglucuronide in the terminal ileum and colon releases glucuronic acid and urobilinogen, which is then reabsorbed back into the liver for further processing.

False Signup and view all the answers

Urobilinogen can be further oxidized into stercobilinogen, which is then converted into stercobilin and excreted in feces, or it can be reabsorbed back into the liver for further processing.

True Signup and view all the answers

The oxidation of urobilinogen forms stercobilin, which is primarily responsible for the yellow color of both urine and feces.

False Signup and view all the answers

The intravascular breakdown of red blood cells accounts for approximately 10%-20% of normal red blood cell destruction.

True Signup and view all the answers

When red blood cells break down within blood vessels, haemoglobin is immediately converted into bilirubin diglucuronide and excreted in urine.

False Signup and view all the answers

Excess intravascular breakdown of red blood cells can lead to the accumulation of haemoglobin in the urine, a condition called haemoglobinuria.

True Signup and view all the answers

The destruction of red blood cells in the bloodstream, involving the release of haemoglobin, is a harmful process that causes significant damage to the body.

False Signup and view all the answers

The diagram illustrates the fate of red blood cells from their production in the bone marrow to their destruction in the spleen, liver, and kidneys.

True Signup and view all the answers

The diagram highlights that red blood cells are actively recycled, with their components, such as iron and amino acids, being reused for new molecule synthesis.

True Signup and view all the answers

Study Notes

Red Blood Cell Lifespan and Destruction

Red blood cell lifespan is 100-120 days
Techniques use radioactive tracers (e.g., chromium) to track cell disappearance from circulation
Chromium is labeled to red blood cells and tracked
Radioactive counts of blood samples are taken to determine survival time
Average lifespan of red blood cells in humans is ~120 days

Phagocytosis of Red Blood Cells

Senescent red blood cells (RBCs) are removed from circulation by phagocytosis
Primarily occurs in macrophages in the spleen, liver, and bone marrow
Macrophages recognize senescence markers on RBCs
Cellular components are broken down and reused
Macrophages use enzymes to digest the RBC components

Breakdown of Erythrocytes

Intravascular breakdown (10-20%): Hemoglobin, released into plasma. Bound to haptoglobin. The complex is processed by liver. Excessive intravascular breakdown leads to hemoglobinuria.
Extravascular breakdown (80%): Macrophages phagocytose RBCs. Hemoglobin is broken down into heme and globin. Heme is further processed in the liver to produce bilirubin.
Globin is broken down, amino acids are reused

Bilirubin Metabolism

Heme is converted into bilirubin by macrophages
Unconjugated bilirubin is transported bound to albumin
Conjugated bilirubin is transported into bile, and excreted in feces and urine as stercobilin and urobilin
Any abnormal elevation of bilirubin may indicate specific hepatic or biliary pathologies

Factors Affecting Red Blood Cell Destruction

Hemolytic disorders
Genetic defects impacting RBC structure or function
Immune-mediated reactions
Mechanical damage to RBCs

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Red blood cell destruction and Bilirubin

Red blood cell destruction and Bilirubin

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Questions and Answers

What is the definition of Haematopoiesis?

What are the three sites of blood cell formation during Haematopoiesis?

During which period does Haematopoiesis occur in the yolk sac?

What is the name for the clusters of mesodermal cells in the embryonic yolk sac where Haematopoiesis occurs in the mesoblastic period?

Which organ becomes the major site of Haematopoiesis during the hepatic period?

What is the name for the period of haematopoiesis when the bone marrow becomes the major site of blood cell production?

The thymus gland is an important site for the production of lymphocytes and monocytes during the hepatic period.

During the first five years of life, myeloid Haematopoiesis occurs practically in all bone marrow.

What is the name for the process of blood cell formation that occurs outside the bone marrow, in tissues like the liver and spleen, in certain disease conditions?

What is the name for the pluripotent stem cell found in bone marrow that is a precursor to all blood cells?

The uncommitted bone marrow pluripotent stem cell is considered ______.

Which of the following cytokine(s) are involved in the differentiation of the uncommitted bone marrow pluripotent stem cell into committed bone marrow stem cells?

Which of the following cytokines are involved in the differentiation of the uncommitted bone marrow pluripotent stem cell into committed lymphocyte stem cells?

What specific type of progenitor cell is responsible for producing B and T cells?

Match the following progenitor cells with their corresponding lineage:

What is the name for the earliest discernible mature form of a particular blood cell that is still actively mitotic?

Blast cells are the mature, non-dividing forms seen in circulation.

Which of the following are characteristics of the differentiation of a blast cell into a mature blood cell?

What is the function of the SCF cytokine?

What is the scientific consensus regarding the origin of all blood cells?

The hemocystoblast actively differentiates into committed stem cells when stimulated by specific hormones or ligands.

Committed stem cells are capable of dividing indefinitely and can give rise to all types of blood cells.

The lifespan of red blood cells is measured by observing the disappearance of a tracer substance, known as a 'label,' from the bloodstream.

Which tracer substance is frequently used for measuring red blood cell lifespan?

How long is the average lifespan of red blood cells in human circulation?

What is the process by which senescent red blood cells are removed from circulation?

Which of the following are sites where phagocytosis of senescent red blood cells mainly occurs?

Macrophages can recognize and engulf only red blood cells, as they are unable to distinguish them from other types of cells.

Which of the following are senescence markers that macrophages recognize on worn-out red blood cells?

What happens to the components of a red blood cell after it's phagocytosed?

The aging process of red blood cells is characterized by a decrease in both metabolic and structural alterations, resulting in an overall increase in cell function.

The decrease in metabolic activity of red blood cells is primarily due to the loss of specific enzymes, such as aspartate aminotransferase and esterase.

The accumulation of oxidative stress within red blood cells is a natural process that doesn't contribute to their aging and eventual removal.

The relative contribution of senescence signals to the phagocytosis of red blood cells is well-understood and fully characterized.

What percentage of red blood cell phagocytosis occurs intravascularly?

What percentage of red blood cell phagocytosis is attributed to macrophages?

Which of the following are tissues where macrophages are found and play a significant role in phagocytosing red blood cells?

The term 'reticuloendothelial system' was originally coined to encompass all macrophages in the body, based on their shared origin from monocytes.

The current understanding of the monocyte-macrophage system (MMS) now recognizes the separate origins and functions of macrophages throughout the body.

What happens to the haemoglobin molecule when a red blood cell is phagocytosed by a macrophage?

What is the purpose of the heme molecule being oxidized by the enzyme microsomal haem oxygenase?

Biliverdin is a straight-chain molecule while bilirubin is a cyclic molecule.

Where is iron stored in macrophages, making it available for the synthesis of new heme?

What enzyme converts biliverdin to bilirubin?

Increased serum bilirubin levels in adults are typically associated with a significant increase in red blood cell destruction.

Elevated serum bilirubin levels in newborns are always indicative of a significant increase in red blood cell destruction.

What condition can arise in newborns with excessive serum bilirubin levels?

Treatment options for kernicterus in newborns include blue light therapy and synthetic porphyrins that contain tin or zinc instead of iron.

Bilirubin is a water-soluble molecule and is transported in the blood free from albumin.

What is the upper limit of normal bilirubin concentration in the blood?

What condition arises when the bilirubin concentration in the blood exceeds 2 mg/dL?

Bilirubin is removed from the blood primarily by the kidneys.

The uptake of bilirubin by hepatocytes in the liver involves the breakdown of the albumin-bilirubin bond, with albumin remaining in the plasma.

What happens when bilirubin is not conjugated in the liver?

Gilbert's disease is a liver disorder that is often caused by a deficiency in the uptake of bilirubin by hepatocytes.

The conjugation of bilirubin in the liver involves the binding of bilirubin to cytoplasmic proteins, such as ligands and 2-proteins.

What is the main function of ligands and 2-proteins in the liver?

The conjugation of bilirubin is a quick process, occurring within minutes.

What is the primary mechanism by which cells neutralize unwanted compounds?

The conjugation of bilirubin involves the addition of xylose, glucose, or glucuronic acid to bilirubin, rendering it more hydrophilic and easier to excrete.

The enzyme uridine diphosphate glucuronosyl transferase, or UDP-glucuronosyl transferase, catalyzes the conjugation of bilirubin with glucuronic acid.

What is the condition where unconjugated bilirubin accumulates in the blood due to a deficiency in the enzyme responsible for conjugating it?

The excretion of conjugated bilirubin involves the active transport of conjugated bilirubin from the liver into the bile canaliculi, forming the bile duct.

In Dubin-Johnson syndrome, the accumulation of conjugated bilirubin in the liver is caused by a deficiency in the excretion of conjugated bilirubin into bile.

What is the name for the process by which bilirubin is reabsorbed in the small intestine, transported back to the liver, and re-excreted without further conjugation?

The breakdown of bilirubin diglucuronide in the terminal ileum and colon releases glucuronic acid and urobilinogen, which is then reabsorbed back into the liver for further processing.

Urobilinogen can be further oxidized into stercobilinogen, which is then converted into stercobilin and excreted in feces, or it can be reabsorbed back into the liver for further processing.

The oxidation of urobilinogen forms stercobilin, which is primarily responsible for the yellow color of both urine and feces.

The intravascular breakdown of red blood cells accounts for approximately 10%-20% of normal red blood cell destruction.

When red blood cells break down within blood vessels, haemoglobin is immediately converted into bilirubin diglucuronide and excreted in urine.

Excess intravascular breakdown of red blood cells can lead to the accumulation of haemoglobin in the urine, a condition called haemoglobinuria.

The destruction of red blood cells in the bloodstream, involving the release of haemoglobin, is a harmful process that causes significant damage to the body.

The diagram illustrates the fate of red blood cells from their production in the bone marrow to their destruction in the spleen, liver, and kidneys.

The diagram highlights that red blood cells are actively recycled, with their components, such as iron and amino acids, being reused for new molecule synthesis.

Study Notes

Red Blood Cell Lifespan and Destruction