Hematopoiesis and Erythropoiesis Flashcards

Flashcards generated from lecture notes on hematopoiesis, erythropoiesis. Covers blood cell formation, maturation, and related metabolic processes.

What is Hematopoiesis?

A continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation, and maturation.

During which phase of hematopoietic development does hematopoiesis first begin and where?

Mesoblastic phase, beginning around the 19th day of embryonic life in the mesoderm of the yolk sac.

What characterizes the hepatic phase of hematopoietic development?

Recognizable clusters of developing erythroblasts, granulocytes, and monocytes, and the beginning of definitive hematopoiesis.

What marks the start of definitive hematopoiesis during the hepatic phase?

Developing erythroblasts signal the beginning of definitive hematopoiesis with a decline in primitive hematopoiesis of the yolk sac

At what stage does myeloid activity become apparent and where does it occur?

Medullary (myeloid) phase, occuring in the medulla of the bone (bone marrow cavity) prior to the fifth month of fetal development.

What are the two major components of adult bone marrow?

Red marrow (hematopoietically active) and yellow marrow (hematopoietically inactive, composed primarily of adipocytes).

What is the role of Kupffer cells in the liver related to hematopoiesis?

They remove senescent cells and foreign debris from the blood and secrete mediators that regulate protein synthesis in hepatocytes.

What is the primary function of the thymus in the hematopoietic system?

It is where T cell progenitors migrate from the bone marrow for further maturation.

What are Colony-Forming Units - Spleen (CFU-S) now referred to?

Now refers to the committed myeloid progenitors or colony-forming unit - granulocyte, erythrocyte, monocyte, and megakaryocyte (CFU-GEMM) which are capable of giving rise to multiple lineages of blood cells

Name two major types of Hematopoietic progenitor cells?

Non-committed or unidifferentiated hematopoietic stem cells and committed progenitor cells

What is the role of cytokines and growth factors in hematopoiesis?

They regulate the proliferation, differentiation, and maturation of hematopoietic progenitor cells (HPCs).

Give examples of cytokines and Groth factors involved in hematopoiesis:

Interleukins (ILs), lymphokines, monokines, chemokines, colony-stimulating factors, Erythropoietin (EPO), Thrombopoietin: (TPO)

How do cytokines prevent hematopoietic precursor cells from dying?

By inhibiting apoptosis, stimulating them to divide, and regulating cell differentiation into various cell lineages.

What is the function of Erythropoietin (EPO)?

Serves to recruit CFU-E from the BFU-E compartment, prevents apoptosis of erythroid progenitors, and induces Hgb synthesis

What are the major categories of Leukopoiesis?

Myelopoiesis and Lymphopoiesis

What earlier influences are including Megakaryopoiesis?

GM-CSF, IL-3, IL-6, IL-11, KIT ligand, TPO

Where does Erythropoiesis occur?

Occurs in the bone marrow

What is erythron?

The name given to the collection of all stages of erythrocytes throughout the body which conveys/covets a unified functional tissue

Name the Erythroid precursors in order of maturity

Pronormoblast, Basophilic normoblast, Polychromatophilic normoblast, Orthochromic normoblast, Reticulocyte, Erythrocyte

What is the Nucleus-to-Cytoplasm ratio (N:C)?

The stage of maturation of any blood cell is determined by careful examination of the nucleus and cytoplasm and qualities of greatest importance in RBC identification

Describe general trends in RBC maturation

Reduction in cell volume, condensation of chromatin, decrease in Nucleus:Chromatin ratio, loss of nucleoli, cytplasm's color changes from blue to gray-blue to salmon pink

What stimulates RBC production?

Hypoxia – the stimulus to RBC production, Primary O2-sensing system is located at the peritubular fibroblast of the kidney

What are the 3 major effects of Erythropioetin (EPO)?

Early release of reticulocytes, prevents apoptopic cell death, Reduces time needed for cell maturation in the bone marrow

What mechanisms are involved in RBC destruction?

Macrophage-mediated hemolysis (extravascular) and Mechanical hemolysis (intravascular).

What cellular process is crucial for RBC survival, especially when navigating the microvasculature?

Membrane deformability, allowing RBCs to squeeze through tiny capillaries to deliver O2 to cells and tissues.

What conditions can decrease membrane deformability?

Decreased levels of ATP and Accumulation/increase of deposition of membrane calcium.

What biochemical components comprise the RBC membrane?

52% protein, 40% lipids, 8% carbohydrates

What are the main Integral proteins?

Glycoporins (A+ , B, C , and D) and Anion exchange-channel protein (band 3)

What is the function of Spectrin?

Principal structural element of the RBC membrane cytoskeleton, constitutues 25 - 30% of the mass of RBC membrane proteins, forms a filamentous network required for blood cells to maintain their shape/elasticity, ghost of the RBC

What lipids are found in external layer of the membrane?

Rich in glycolipids, glycoproteins, and choline phospholipids

What lipids are found in the Internal cytoplasmic later of the membrane?

Rich in amino phospholipids

What are the main Peripheral proteins?

Spectrin, ankyrin, adducin, band 4.1

What conditions are associated with decreased phosphorylated spectrin or altered spectrin?

Hereditary spherocytosis and G6PD deficiency.

What are the function of Band 3, Peripheral proteins of the RBC membrane cytoskeleton?

Anion exchange-channel protein, Major RBC transmembrane protein, has 2 distinct domains: the transmembrane and cytoplasmic

What are the conditions ass. with abnormalities of RBC membrane lipids?

Liver disease, thalassemia, iron-deficiency anemia, sickle cell disease, megaloblastic anemia, abetalipoproteinemia, and LCAT enzyme deficiency

What are poikilocytes associated with abnormalities of RBC membrane lipids?

Codocytes/target cells, associated with liver disease, thalassemia, iron-deficiency anemia, sickle cell disease, and megaloblastic anemia and Acanthocytes/spur cells, associated with abetalipoproteinemia and LCAT enzyme deficiency

What is the normal reference range % of Reticulocytes in Adults?

Adults: 0.5 - 2.0%

What is the normal reference range % of Reticulocytes in Newborns?

Newborns: 2.5 - 6%

Define Agglutination & Rouleaux

Agglutination-RBCs aggregate or clump together into random clusters/masses on the periphera blood smear, Rouleaux-RBCs appear as a stack of coins on the peripheral blood smear

What causes Aggultination and what diseases does it show in?

Results from antigen-antibody reaction within the body, Seen in patients with cold hemagglutinin dss. and paroxysmal cold hemoglobinuria

What causes Rouleaux Formation and what diseases does it show in?

Results from elevated blood antigen protein levels (e.g., globulins and fibrinogen), Seen in patients with multiple myeloma and Waldenstrom’s macroglobulinemia

What are the inclusions that are only visible with a supravital stain?

Reticulocytes and Hemoglobin H

What are the two mechanisms of RBC destruction?

Macrophage-mediated hemolysis and Mechanical hemolysis

What are the RBC metabolic pathways?

EMBDEN-MEYERHOF PATHWAY, HEXOSE MONOPHOSPHATE SHUNT, LUEBERING-RAPAPORT PATHWAY, METHEMOGLOBIN REDUCTASE PATHWAY

What is the function of EMBDEN-MEYERHOF PATHWAY?

Anaerobic breakdown of glucose or glycolysis, ~40% of the ATP is generated by the E-MP, The metabolism of glucose results in the net generation of 2 ATP molecules, this type of ATP synthesis pathway is less efficient than the Krebs cycle, but it provides sufficient ATP for RBC requirements

What is the function of HEXOSE MONOPHOSPHATE SHUNT?

An oxidative pathway in contrast to EMP, HMP is also called the phosphogluconate pathway, Approx. 5 - 10% of the glucose is metabolized by the HMP, this pathway produced the pyridine nucleotide NADPH from NADP+, NADPH, together with glutathione, provides the main line of defense for the RBC againt oxidative stress or injury (e.g., H2O2 and other oxidants)

What is the function of a LUEBERING-RAPAPORT PATHWAY?

Also called the Luebering-Rapaport shunt, is a metabolic pathway in mature erythrocytes involving the formation of 2,3-diphosphoglycerate (2,3-DPG), which regulates O2 release from Hgb and delivery to tissues

What is the function METHEMOGLOBIN REDUCTASE PATHWAY?

NADH-dependent methemoglobin reduction, also called diaphorase I pathway, more properly called cytochrome bS reductase (CytbSR), the enzyme within the erythrocyte maintains Hgb in the reduced state (non-methemoglobin, ferrous) state

Name Newborn screening program in the Philippines currently includes screening for what 6 disorders?

Congenital hypothyroidism (CH), Congenital adrenal hyperplasia (CAH), Phenylketonuria (PKU), Glucose-G-phosphate dehydrogenase (G6PD) deficiency, Galactosemia (GAL), Maple syrup urine dss. (MSUD)

What components make up the Hemoglobin Structure?

Heme and Globin portions

What is the Heme structure?

The key component of Hgb molecule, consists of a ring-like protoporphyrin IX molecule with a central atom of ferrous iron (Fe2+)

What is the Globin structure?

The protein component of the Hgb molecule, the predominant adult Hgb (Hgb A) molecule is composed of 4 globin chains (tetramer): 2 alpha chains, 2 beta chains

What is the most predominant hemoglobin in adults?

Hgb A

What are the Heme and Globin disorders?

Heme-Porphyria, Globin-Thalassemia, Hemoglobinopathies

What is Porphyria?

Porphyrins build up and affect the skin and nervous system

What is Thalassemia?

A quantitative defect: Defects or mutations affecting the globin chain production

What is Hemoglobinopathies?

A qualitative defect: Defects or mutations affecting the globin chain structure

In cells, ferrous iron can react with peroxide via the Fenton reaction, what does this form?

This forms highly reactive O2 molecules (free hydroxyl radicals - potent oxidizing agents) which are able to cause oxidative reactions with lipids, proteins, and nucleic acids, which leads to cellular injury

What is Ferrous form of iron (Fe2+)?

Functional form of iron, essential for RBC production, DNA synthesis, electron transport, and O2 transport, 70% stored in RBCs and muscles (part of heme), Easily absorbable in the gut

What is Ferritic form of iron (Fe3+)?

Iron bound to transferrin (1 Tf = 2 Fe3+), Ass. with ferritin and hemosiderin (iron storage), Iron in methemoglobin cannot transport O2, Non-heme iron found in plant food sources, Not well absorbed

What is DMT1 related to the Absorption of iron in the intestines?

Ferric iron (Fe3+) in the intestinal lumen, is reduced to ferrous iron (Fe2+) before transport across the luminal membrane of the enterocyte by the ferrireductase, duodenal cytochrome b (Dcytb), It is then able to be transported through the luminal membrane of the enterocyte cytoplasm by divalent metal transporter 1 (DMT1)

What is the negative feedback loop for Feedback mechanisms in iron absorption?

When the body has adequate iron stores, the liver will produce the regulatory protein, hepcidin, which binds to ferroportin, leading to its inactivation, Iron absorption in the body decreases

What is the positive feedback loop for Feedback mechanisms in iron absorption?

When the body’s iron begins to drop, the liver senses that change and decreases hepcidin production, As a result, ferroportin is once again active and is able to transport iron into the blood

Where does the synthesis of heme occur?

Mitochondria and cytoplasm of bone marrow erythroid precursor cells.

What are Porphyrias?

Defects (congenital deficiencies) in enzymes of heme biosynthesis pathway underlie biochemical abnormalities, which occurs in porphyrias (accumulation of precursor molecules)

Name the Hemoglobin Reference Values range for Men

13.5 - 18.0 g/dL (135 - 180 g/L)

Name the Hemoglobin Reference Values range for Women

12.0 - 15.0 g/dL (120 - 150 g/L)

What is the relationship between high levels of CO2 and Hgb releases?

The Bohr effect explains how high levels of CO2 helps Hgb release (dissociate) O2 in tissues that need O2

How do dysfunctional HgBs affect oxygen transport?

Dysfunctional HgBs are unable to transport O2 and May accumulate to toxic levels after exposure to certain drugs or environmental chemicals/gases

Methemoglobin cannot carry O2, why?

because oxidized ferric iron cannot bind it & An increase in MethB levels results in decreased O2 delivery to tissues

Sulfhemoglobin can not be converted back to Hgb A, why?

It persists fro the life of the cell

Carbon monoxide (CO), what is the affinity of CO for Hgb compared to O2?

The affinity of CO for Hgb is 240 times that of O2

What does Arterial and Venous Blood with carboxyhemoglobin exhibit?

exhibits a cherry red color

What is Cyanmethemoglobin Method?

The standard reference method for Hgb assay, All forms of Hgb except sulfhemoglobin are converted to cyanmethemoglobin