hemoglobin and rbc by dr avinash

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HEMOPOIESIS & ERYTHROPOIESIS : 

HEMOPOIESIS & ERYTHROPOIESIS By Dr. Avinash S. Ingle, MD Associate professor of Physiology

METAMORPHOSIS : 

METAMORPHOSIS

HEMOPOIESIS: INTRO : 

HEMOPOIESIS: INTRO Hemo: Referring to blood cells Poiesis: “The development or production of” The word Hemopoiesis refers to the production & development of all the blood cells: Erythrocytes: Erythropoiesis Leucocytes: Leucopoiesis Thrombocytes: Thrombopoiesis. Begins in the 20th week of life in the fetal liver & spleen, continues in the bone marrow till young adulthood & beyond!

SITES OF HEMOPOIESIS : 

Appendicular skeleton: Bones of the Upper & Lower limbs In Adults active hemopoietic marrow is found only in: The axial skeleton The proximal ends of the appendicular skeleton. SITES OF HEMOPOIESIS Active Hemopoietic marrow is found, in children throughout the: Axial skeleton: Cranium Ribs. Sternum Vertebrae Pelvis

STEM CELL THEORY : 

STEM CELL THEORY The dazzling array of all the blood cells are produced by the bone marrow. They all come from a single class of primitive mother cells called as: PLURIPOTENT STEM CELLS. These cells give rise to blood cells of: Myeloid series: Cells arising mainly from the bone marrow. Lymphoid series: cells arising from lymphoid tissues.

CLONAL HEMOPOIESIS : 

CLONAL HEMOPOIESIS PLURIPOTENT STEM CELL STEM CELL MULTIPLICATION COMMITTMENT COMMITTED STEM CELL COMMITTED STEM CELL MULTIPLICATION PROGENITOR CELL CFU: COLONY FORMING UNIT

CLONAL HEMOPOIESIS: (Contd) : 

CLONAL HEMOPOIESIS: (Contd) COLONY FORMING UNIT (CFU) INTERMEDIATE BLAST CELLS MATURE BLOOD CELLS END CELLS: FINITE LIFE SPAN MORPHOLOGICALLY RECOGNIZABLE

HEMOPOIESIS: AN OVERVIEW : 

HEMOPOIESIS: AN OVERVIEW

STEM CELLS : 

STEM CELLS These cells have extensive proliferative capacity and also the: Ability to give rise to new stem cells (Self Renewal) Ability to differentiate into any blood cells lines (Pluripotency) They grow and develop in the bone marrow. The bone marrow & spleen form a supporting system, called the “hemopoietic microenvironment”

STEM CELLS: Types : 

Pluripotent Stem cells: Has a diameter of 18 – 23 μ. Giving rise to: both Myeloid and Lymphoid series of cells Capable of extensive self-renewal. Myeloid Stem cells: Generate myeloid cells: Erythrocytes Granulocytes: PMNs, Eosinophils & Basophils. Thrombocytes. Lymphoid Stem cells: Giving rise only to: Lymphocytes: T type mainly. STEM CELLS: Types

PROGENITOR CELLS : 

PROGENITOR CELLS Committed stem cells lose their capacity for self-renewal. They become irreversibly committed. These cells are termed as “Progenitor cells” They are regulated by certain hormones or substances so that they can: Proliferate Undergo Maturation.

CELL LINE REGULATORS : 

CELL LINE REGULATORS

BLOOD CELLS: DEVELOPMENT : 

BLOOD CELLS: DEVELOPMENT

HEMOPOIESIS: REVIEW I : 

HEMOPOIESIS: REVIEW I Hemopoiesis: Production of blood cells. Site: Predominantly in the Bone Marrow. Both axial & appendicular skeletons. Erythropoiesis: Production of Erythrocytes. Leucopoiesis: Production of Leucocytes. Thrombopoiesis: Production of Thrombocytes.

HEMOPOIESIS: REVIEW II : 

HEMOPOIESIS: REVIEW II Cell lines: Pluripotent Stem Cell Progenitor Stem Cells: Committed Proerythroblasts Myeloblasts Monoblasts Lymphoid cells Megakaryoblasts

ERYTHROPOIESIS: SITES/PHASES : 

ERYTHROPOIESIS: SITES/PHASES INTRAUTERINE LIFE: INTRAVASCULAR PHASE: Upto 3rd month of Intra Uterine Life. Endothelial cells = = = RBCs HEPATIC PHASE: 3rd to 5th month IUL Liver & Spleen nRBCs from Mesenchymal cells. MYELOID PHASE: From 5th month of IUL onwards.

ERYTHROPOIESIS: SITES/PHASEScontd. : 

POST NATAL LIFE: CHILDREN: Predominantly Red Bone Marrow of skeleton: Axial & Appendicular. ADULTS: Red Bone Marrow of Axial Skeleton. ERYTHROPOIESIS: SITES/PHASEScontd.

ERYTHROPOIESIS : 

ERYTHROPOIESIS

FACTORS REGULATINGERYTHROPOIESIS : 

FACTORS REGULATINGERYTHROPOIESIS SINGLE MOST IMPORTANT REGULATOR: “TISSUE OXYGENATION” BURST PROMOTING ACTIVITY ERYTHROPOIETIN IRON VITAMINS: Vitamin B12 Folic Acid MISCELLANEOUS

ERYTHROPOIETIN : 

ERYTHROPOIETIN A hormone produced by the Kidney. A circulating Glycoprotein Nowadays available as Synthetic Epoietin Acts mainly on CFU – E. Increases the number of: Nucleated precursors in the marrow. Reticulocytes & Mature Erythrocytes in the blood.

VITAMINS : 

VITAMINS B12: Cyanocobalamine & Folic Acid: Is also called Extrinsic Factor of Castle. Needs the Intrinsic Factor from the Gastric juice for absorption from Small Intestine. Deficiency causes Pernicious (When IF is missing) or Megaloblastic Anemia. Stimulates Erythropoiesis Is found in meat & diary products.

IRON : 

IRON Essential for the synthesis of Hemoglobin. Deficiency causes Microcytic, Hypochromic Anemia. The MCV, Color Index & MCH are low.

ERYTHROPOIESIS: SEQUENTIAL CHANGES : 

ERYTHROPOIESIS: SEQUENTIAL CHANGES I II III IV V VI PRONORMOB L A S T E AR L Y N B L A S T I N T E R N B L A S T L A T E N B L A S T R E T I C U L OC Y T E MA T UR E RB C MITOCHONDRIA BASOPHILIA HEMOGLOBIN

ERYTHROID PROGENITOR CELLS : 

ERYTHROID PROGENITOR CELLS BFU-E: Burst Forming Unit – Erythrocyte: Give rise each to thousands of nucleated erythroid precursor cells, in vitro. Undergo some changes to become the Colony Forming Units-Erythrocyte (CFU-E) Regulator: Burst Promoting Activity (BPA)

ERYTHROID PROGENITOR CELLS : 

CFU-E: Colony Forming Unit- Erythrocyte: Well differentiated erythroid progenitor cell. Present only in the Red Bone Marrow. Can form upto 64 nucleated erythroid precursor cells. Regulator: Erythropoietin. Both these Progenitor cells cannot be distinguished except by in vitro culture methods. ERYTHROID PROGENITOR CELLS

NORMOBLASTS : 

NORMOBLASTS ERYTHRON: Nucleated erythroid precursors Reticulocytes. NORMOBLASTIC: Normal erythropoiesis. MEGALOBLASTIC: Vit B12 deficiency.

Normoblastic Precursors : 

Normoblastic Precursors PROERYTHROBLAST: Large cell: 15 – 20 Microns in diameter. Cytoplasm is deep violet-blue staining Has no Hemoglobin. Large nucleus 12 Microns occupies 3/4th of the cell volume. Nucleus has fine stippled reticulum & many nucleoli.

Normoblastic Precursors : 

EARLY NORMOBLAST: Smaller in size. Shows active Mitosis. No nucleoli in the nucleus. Fine chromatin network with few condensation nodes found. Hemoglobin begins to form. Cytoplasm still Basophilic. Normoblastic Precursors

Normoblastic Precursors : 

INTERMEDIATE NORMOBLAST: Has a diameter of 10 – 14 Microns. Shows active Mitosis. Increased Hemoglobin content in the cytoplasm Cytoplasm is Polychromatophilic. Normoblastic Precursors

Normoblastic Precursors : 

LATE NORMOBLAST: Diameter is 7 – 10 Microns. Nucleus shrinks with condensed chromatin. Appears like a “Cartwheel” Cytoplasm has a Eosinophilic appearance. Normoblastic Precursors

Normoblastic Precursors : 

RETICULOCYTE: The penultimate stage cell. Has a fine network of reticulum like a heavy wreath or as clumps of dots This is the remnant of the basophilic cytoplasm, comprising RNA. In the Neonates, Count is 2 – 6/Cu.mm. Falls to <1 in the first week of life. Reticulocytosis is the first change seen in patients treated with Vit B12 Normoblastic Precursors

Normoblastic Precursors : 

MATURE ERYTHROCYTE: Biconcave disc. No nucleus. About One-third filled with Hemoglobin. Normoblastic Precursors

Regulation of Erythropoiesis : 

Regulation of Erythropoiesis CFU – E Proerythroblasts Mature Erythrocytes Tissue Oxygenation Factors decreasing: Hypovolemia Anemia Poor blood flow Pulmonary Disease ERYTHROPOIETIN Decreases Stimulates An example of a Negative feed back mechanism

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