Erythropoiesis and Blood Disorders Quiz

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Questions and Answers

What primarily stimulates erythropoiesis?

  • Erythropoietin hormone (correct)
  • Liver enzymes
  • Testosterone
  • Platelet count

Where is the majority of erythropoietin produced in the body?

  • Liver
  • Bone marrow
  • Kidneys (correct)
  • Spleen

Which of the following conditions can lead to hypoxia?

  • Low red blood cell count (Anemia) (correct)
  • High blood pressure
  • Increased white blood cell count
  • Excessive hydration

Which factor stimulates erythropoietin production apart from hypoxia?

<p>Norepinephrine (C)</p> Signup and view all the answers

What role does erythropoietin play in the body?

<p>Stimulates early stem cell growth (D)</p> Signup and view all the answers

What is the role of plasmin in the body?

<p>It digests fibrin fibers. (B)</p> Signup and view all the answers

Which of the following is essential for the activation of certain clotting factors?

<p>Calcium ions (C)</p> Signup and view all the answers

What condition is caused by a deficiency of platelets?

<p>Thrombocytopenia (D)</p> Signup and view all the answers

What effect does warfarin have on the body?

<p>Interferes with vitamin K action. (D)</p> Signup and view all the answers

What condition is described by the liver's inability to process bilirubin effectively, leading to bilirubin accumulation?

<p>Jaundice (A)</p> Signup and view all the answers

What is a potential cause of post-hepatic jaundice?

<p>Obstruction of bile flow (B)</p> Signup and view all the answers

Which drug inhibits thrombin by enhancing the activity of antithrombin III?

<p>Heparin (C)</p> Signup and view all the answers

Which type of jaundice is characterized by an unconjugated hyperbilirubinaemia due to excessive breakdown of red blood cells?

<p>Pre-hepatic jaundice (C)</p> Signup and view all the answers

What is the fate of most bilirubin after conjugation in the liver?

<p>Converted to urobilinogen and excreted in feces (D)</p> Signup and view all the answers

Which condition may prevent infants from effectively eliminating bilirubin, leading to jaundice?

<p>Infantile hemolytic disease (C)</p> Signup and view all the answers

Which condition is associated with high erythropoietin levels and polycythemia?

<p>High altitude (C)</p> Signup and view all the answers

What is the primary storage form of iron in the liver?

<p>Ferritin (D)</p> Signup and view all the answers

What vitamin is essential for the absorption of Vitamin B12?

<p>Intrinsic Factor (A)</p> Signup and view all the answers

Which vitamin deficiency leads to megaloblastic anemia?

<p>Folic Acid (A)</p> Signup and view all the answers

What is the primary role of erythropoietin?

<p>To stimulate red blood cell production (C)</p> Signup and view all the answers

What leads to the development of pernicious anemia?

<p>Intrinsic Factor deficiency (A)</p> Signup and view all the answers

Which of these components is NOT part of hemoglobin's iron content?

<p>Transferrin (C)</p> Signup and view all the answers

Which factor does NOT affect erythropoiesis?

<p>Fever (C)</p> Signup and view all the answers

What role does albumin play in relation to bilirubin?

<p>It increases the solubility of bilirubin. (C)</p> Signup and view all the answers

What characterizes prehepatic jaundice?

<p>Excess production of bilirubin (B)</p> Signup and view all the answers

What is the normal range of bilirubin in the blood?

<p>1-16 µmol/l (0.1-1 mg/dl) (B)</p> Signup and view all the answers

Which condition is associated with intrahepatic jaundice?

<p>Generalized liver dysfunction (D)</p> Signup and view all the answers

What bilirubin level is indicative of jaundice?

<p>2 mg/dl (D)</p> Signup and view all the answers

What type of cells are included in the category of granular leukocytes?

<p>Eosinophils and neutrophils (B)</p> Signup and view all the answers

What symptom is characteristic of posthepatic jaundice?

<p>Pale colored stools (B)</p> Signup and view all the answers

Which cell type is responsible for forming platelets?

<p>Megakaryocytes (C)</p> Signup and view all the answers

What is a common treatment for neonatal jaundice with high bilirubin levels?

<p>Phototherapy (C)</p> Signup and view all the answers

What is a progenitor cell that can form erythrocytes called?

<p>CFU-E (B)</p> Signup and view all the answers

Which condition might lead to prehepatic jaundice?

<p>Hemolytic disease of the newborn (D)</p> Signup and view all the answers

What typically follows a complete obstruction in posthepatic jaundice?

<p>Absence of urobilin in urine (A)</p> Signup and view all the answers

Which of the following is an agranular leukocyte?

<p>T lymphocyte (A)</p> Signup and view all the answers

What happens to the nucleus of a red blood cell during its maturation?

<p>It is ejected. (C)</p> Signup and view all the answers

What is the normal concentration of unconjugated bilirubin in plasma?

<p>0.5 mg/dL (C)</p> Signup and view all the answers

What is the consequence of excessive breakdown of extravasated blood?

<p>Prehepatic jaundice (B)</p> Signup and view all the answers

Flashcards

Erythropoiesis Stimulation

Erythropoiesis, the production of red blood cells (RBCs), is triggered by erythropoietin (EPO), a hormone primarily produced by the kidneys.

Erythropoietin Production Trigger

Erythropoietin (EPO) release is stimulated by low oxygen levels in the blood (hypoxia) which can arise from various factors like low RBC count, hemorrhage, high altitude, heart failure, or lung disease.

Kidney's Role in EPO

EPO is mainly produced by fibroblast cells in the kidney's cortex and outer medulla. These cells are highly sensitive to low oxygen levels and release EPO in response.

EPO's Composition and Origin

Erythropoietin is a glycoprotein mainly produced by the renal cortex of the kidneys. A small amount also comes from the liver.

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Hypoxia's effect on EPO

When tissue oxygen levels are low, hypoxia-inducible factor-1 (HIF-1) is increased influencing EPO production.

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What is Jaundice?

Jaundice, also known as bilirubinemia, is a condition characterized by a yellowing of the skin and whites of the eyes due to an excess of bilirubin in the blood.

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Types of Jaundice

There are three main types of jaundice: pre-hepatic, intrahepatic, and post-hepatic. Each type arises from a different point in the bilirubin processing pathway.

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Pre-Hepatic Jaundice

Pre-hepatic jaundice occurs when there is excessive breakdown of red blood cells, overwhelming the liver's ability to process bilirubin. This results in high levels of unconjugated bilirubin in the blood.

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Intrahepatic Jaundice

Intrahepatic jaundice (also called hepatocellular jaundice) is caused by liver dysfunction. The liver loses its ability to conjugate bilirubin, leading to an accumulation of both conjugated and unconjugated bilirubin.

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Post-Hepatic Jaundice

Post-hepatic jaundice results from an obstruction in the bile ducts, preventing the flow of conjugated bilirubin into the intestines. This leads to a build-up of conjugated bilirubin in the blood.

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Unconjugated Bilirubin

Bilirubin that is not yet attached to a molecule (like glucuronic acid) in the liver. It's not water-soluble and is bound to albumin in the blood.

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Conjugated Bilirubin

When bilirubin is attached to a molecule, like glucuronic acid, in the liver, becoming water-soluble and ready for excretion.

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Neonatal Jaundice

Common in newborns, especially premature infants, resulting from immature liver function and excess bilirubin production.

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Kernicterus

A serious complication of neonatal jaundice where high bilirubin levels damage the brain, leading to neurological problems.

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Phototherapy

Using light to convert bilirubin into a water-soluble form, allowing it to be excreted, used to treat neonatal jaundice.

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Plasminogen's Role

Plasminogen, a plasma protein, transforms into the potent enzyme plasmin when activated.

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Plasmin's Action

Plasmin actively dissolves fibrin fibers, the core of blood clots, and also breaks down several clotting factors, like fibrinogen and Factor VIII.

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What Happens to the Clot?

The process of dissolving a blood clot through plasmin activity is called fibrinolysis. It's crucial for preventing excessive clotting and ensuring normal blood flow.

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Causes of Excessive Bleeding

Deficiencies in various blood-clotting factors can lead to excessive bleeding. This can be from lack of vitamin K, hemophilia, or a shortage of platelets.

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How Does Vitamin K Affect Clotting?

Vitamin K is crucial for activating several crucial blood clotting factors - Prothrombin, Factor VII, Factor IX, Factor X, and Protein C. Deficiency can hinder clotting.

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Bilirubin Binding

Unconjugated bilirubin, a breakdown product of heme, binds to albumin in the blood.

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Why Bilirubin Binds Albumin

Binding to albumin increases bilirubin's solubility in blood and prevents it from damaging tissues.

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Normal Bilirubin Range

The normal range for bilirubin in blood is 1 to 16 µmol/L (0.1 to 1 mg/dL).

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Jaundice

Jaundice, or yellowing of the skin and eyes, can occur when bilirubin levels exceed 2 mg/dL.

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Red Blood Cell Characteristics

Red blood cells (erythrocytes) are biconcave, lack a nucleus, and contain hemoglobin for oxygen transport.

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Scanning Electron Microscopy (SEM)

SEM is a powerful technique that provides detailed 3D images of cell surfaces.

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Blood Cell Formation

Pluripotent stem cells in the bone marrow differentiate into various blood cells, including red blood cells, white blood cells, and platelets.

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Red Blood Cell Production

Red blood cell production, called erythropoiesis, is stimulated by erythropoietin (EPO), a hormone produced mainly by the kidneys.

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What stimulates erythropoiesis?

Erythropoiesis, the production of red blood cells (RBCs), is stimulated by the hormone erythropoietin (EPO), which is primarily produced by the kidneys.

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What conditions lead to high erythropoietin levels?

Conditions like anemia, high altitude, heart failure, and lung disease all result in low oxygen levels in the blood, leading to increased erythropoietin production by the kidneys to stimulate red blood cell production.

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Hemoglobin's role

Hemoglobin is a protein found in red blood cells that is responsible for carrying oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.

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Types of Hemoglobin

There are different types of hemoglobin. Hb A is the most common type in adults, Hb A2 is a minor component, and Hb F is the fetal form of hemoglobin.

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Where is iron stored?

Iron, an essential component of hemoglobin, is stored mainly in the liver as ferritin. Other storage sites are in the spleen and bone marrow.

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What is Apotransferrin?

Apotransferrin is an inactive form of the protein transferrin, which is involved in iron transport. It becomes active when bound to iron, turning into transferrin.

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What factors affect erythropoiesis?

Erythropoiesis is influenced by various factors including iron, vitamins like B12, folic acid, C, protein intake, and erythropoietin.

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What is Intrinsic Factor?

Intrinsic factor is a substance produced in the stomach that is essential for the absorption of Vitamin B12. Its deficiency can lead to pernicious anemia.

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Study Notes

Blood Physiology

  • Blood is a connective tissue in fluid form, considered the fluid of life. It carries oxygen from lungs to body parts and carbon dioxide from body parts to lungs.
  • Blood is red in color. Arterial blood is scarlet red due to oxygenated hemoglobin (HbO2) and venous blood is purple-red due to carbon dioxide.
  • Average blood volume in normal adult is 5 liters. In a newborn, its 450 ml, and increases to 5 liters during puberty. In females, it's slightly less, around 4.5 liters, and roughly 8% of body weight in a healthy young adult (70kg).

Blood Composition

  • Blood consists of two parts:
    • Plasma (55% of blood volume): mainly water (91%), with ions, plasma proteins (albumin, globulin, fibrinogen), nutrients, waste products, gases, and regulatory substances. Plasma has the same ionic composition as interstitial fluid.
    • Formed elements (45% of blood volume): Red blood cells (erythrocytes), White blood cells (leukocytes) and Platelets (thrombocytes).

Functions of Blood

  • Transport of oxygen, carbon dioxide, nutrients, hormones, and waste products.
  • Maintain homeostasis (body temperature, ECF pH).
  • Protect against infection (white blood cells, antibodies).
  • Blood clotting to prevent blood loss.

Blood Cells Formation

  • Erythropoiesis: Formation of red blood cells (RBCs).
  • Leucopoiesis: Formation of white blood cells (WBCs).
  • Thrombopoiesis: Formation of platelets (thrombocytes).

Hematopoiesis

  • Production of blood cells starts in early embryonic life.
  • Different locations throughout development: Yolk sac (early weeks), Liver & spleen & lymph nodes (middle trimester), Bone marrow of all bones (last few months)
  • After birth, bone marrow of flat bones continues RBC production. The shaft of long bones stops producing RBCs at puberty, though the epiphyses continue.

Sites of Active Bone Marrow

  • In adults, red bone marrow is primarily found in the axial skeleton, pelvic and pectoral girdles, and proximal epiphyses of the humerus and femur.

Normal Bone Marrow Conversion

  • Stages in humans: Infancy (<1 year) - all red marrow. Childhood (1-10 years) - centralized red marrow. Adolescence (10-20 years) and Adulthood (>25 years) - centralized yellow marrow with some red in certain sites.

Blood Cell Characteristics

  • Red Blood Cells (RBCs):
    • Biconcave discs, 7.5 µm diameter.
    • Flexible membrane.
    • No mitochondria, ribosomes, or RNA.
    • Anaerobic glycolysis.
    • Life span of 120 days.
    • Normal count 4.7-5.2 million/mm³.
    • Hemoglobin (Hb) concentration 14-16 g/dL.
    • Function: transport oxygen and carbon dioxide, buffer.
  • White Blood Cells (WBCs): Granulocytes (polymorphonuclear leukocytes): Neutrophils (60%), Eosinophils (2%), Basophils (0.4%). Agranulocytes (mononuclear leukocytes): Lymphocytes (30%), Monocytes (5%).
  • Platelets (thrombocytes):
    • Small irregular cell fragments (2-3 µm).
    • Formed in cytoplasm of megakaryocytes.
    • Normal count 150,000-450,000/cu mm of blood.

Erythropoiesis

  • Characterized by: Reduction in cell size. Disappearance of the nucleus. Appearance of hemoglobin.
  • Production is stimulated by erythropoietin (EPO), a hormone produced by the kidneys in response to hypoxia (low oxygen). Hypoxia can be caused by low RBC count (anemia), hemorrhage, high altitude, prolonged heart failure, or lung disease.

Hemoglobin

  • Composed of four globin protein chains (two alpha, two beta).
  • Each globin chain has a heme group.
  • Heme groups contain iron, which binds oxygen.
  • Types of hemoglobin: Hb A (major type in adults), Hb A2, Hb F (fetal hemoglobin).

Iron Metabolism

  • Iron is part of hemoglobin and myoglobin.
  • Most iron is in hemoglobin (~65%).
  • About 1% of iron in various heme compounds.
  • Some iron is in plasma (combined with transferrin).
  • Some iron is stored in the liver as ferritin.

Extravascular RBC Destruction

  • Old or damaged red blood cells are destroyed in the spleen, liver, and bone marrow
  • Components are recycled: Heme → bilirubin; Globin → amino acids, Fe2+.
  • Bilirubin is processed by the liver and excreted in bile.

Jaundice

  • Yellow discoloration of skin/eyes due to bilirubin build up in blood
  • Prehepatic Jaundice: Excessive red blood cell breakdown overwhelms liver's ability to conjugate bilirubin.
  • Intrahepatic Jaundice: Dysfunction of liver cells, preventing bilirubin conjugation.
  • Posthepatic Jaundice: Obstruction of the biliary tree, causing conjugated bilirubin buildup

White Blood Cell Types and Functions

  • Neutrophils and macrophages: Phagocytosis (cellular ingestion of foreign matter or pathogens). Neutrophils are the primary responders present in large numbers during infections
  • Monocytes: Immature cells in the blood, mature into macrophages in tissues; more powerful phagocytes and can survive for months.
  • Eosinophils: Attack and destroy parasites, participate in allergic responses.
  • Basophils: Release heparin (prevents blood clotting) and histamine (related to allergic reactions).
  • Lymphocytes: Responsible for acquired immunity. B lymphocytes produce antibodies, while T lymphocytes directly destroy infected cells and cancer cells.

Hemostasis and Blood Coagulation

  • Hemostasis: Prevention of blood loss when a vessel is ruptured.
    • Vascular constriction (spasm): Immediate narrowing of the vessel to reduce blood flow.
    • Platelet plug formation: Platelets adhere to collagen exposed by injury; thromboxane and ADP release leads to further platelet aggregation.
    • Coagulation (blood clot formation): Cascade of reactions in which fibrinogen is converted into fibrin, forming a mesh that traps blood cells and platelets.
    • Clot retraction: Contraction of platelets to tighten the clot, closing the vessel opening further.
    • Fibrinolysis: The breakdown of the clot by plasmin, which digests fibrin and other clotting factors.

Anticoagulants

  • Substances that inhibit clotting.
  • Intravascular factors: Endothelial surface factors (smoothness, glycocalyx layer and thrombomodulin). Inhibit clotting in normal blood vessels. Prostacyclin and Nitric Oxide produced by healthy endothelial cells inhibit platelet aggregation.
  • In vitro Anti-coagulants: EDTA, Oxalate, Heparin, Sodium Citrate. They prevent clotting in collected blood samples.

Effects of Anemia and Polycythemia

  • Anemia: Reduced RBC count/hemoglobin; decreased blood viscosity. Increased blood flow and cardiac output because of tissue hypoxia. Reduced resistance to blood flow, leading to higher blood flow throughout the tissues and higher cardiac output.

  • Polycythemia: Increased RBC count, increased blood viscosity; more sluggish blood flow. Reduced venous return to the heart.

Blood Disorders

  • Excessive increase in white blood cells in the absence of infection is leukemia. The increase in white blood cells as a result of infection is leukocytosis. Different types of anemia exist, based on the underlying cause such as blood loss, poor diet, or a genetic disorder affecting the red blood cells.
  • Various types of blood disorders can occur (polycythemia, anemia, and others). These are characterized by abnormal or reduced numbers/function of blood cells. Causes can range from deficiencies in nutritional aspects of the diet, or genetic diseases that affect blood cell creation and maintenance. Note: This is not an exhaustive list, but highlights the main categories.

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