ch.09. hematopoietic-system.pptx

Hematopoietic System Kristine Krafts, M.D. Hematopoietic System Lecture Objectives • Describe the developmental stages of erythropoiesis. • Describe the developmental stages of granulopoiesis. • Describe the differences between red marrow and yellow marrow. • List the components of bone marrow str...

Hematopoietic System Kristine Krafts, M.D. Hematopoietic System Lecture Objectives • Describe the developmental stages of erythropoiesis. • Describe the developmental stages of granulopoiesis. • Describe the differences between red marrow and yellow marrow. • List the components of bone marrow stroma. • Explain the concept of colony forming units (CFUs). Hematopoietic System Lecture Outline • Introduction • Erythrocytes • Platelets • Leukocytes • Granulocytes • Agranulocytes Hematopoietic System Lecture Outline • Introduction Hematopoietic Tissue Specialized connective tissue. Derived from mesenchyme. Function: produce new blood cells and remove old ones. Two types of hematopoietic tissue • Myeloid tissue (in bone marrow): produces everything except lymphocytes • Lymphoid tissue (in lymph nodes, spleen): produces lymphocytes Prenatal Hematopoiesis Myeloid Tissue (Bone Marrow) • Bone marrow in adults is found between trabeculae of cancellous (spongy) bone and in the marrow canal of long bones. • Red (hematopoietic) bone marrow is found in flat bones of skull, vertebrae, ribs, pelvis, and ends of long bones. • Yellow bone marrow is found in long bone diaphyses. It is composed of fibrous CT, adipose tissue (yellow color), nerves, and blood vessels. Components of Bone Marrow • Stroma: a connective tissue network which supports the blood-forming cells. • Sinusoids: wide, thin-walled vessels with discontinuous endothelial cells which allow new blood cells to gain access to the bloodstream. • Developing blood cells: red cell precursors, white cell precursors (except lymphoid precursors), and megakaryocytes. Stroma Cells • Fibroblasts • Macrophages • Adipocytes (fat cells) • Osteogenic cells • Endothelial cells Fibers • Type I collagen fibers • Type III collagen (reticular) fibers Bone marrow is present between trabeculae of Bone marrow: trabeculae, hematopoietic tissue Hematopoie sis Hematopoiesis • All blood cells arise from a single type of pluripotent stem cell (which is selfrenewing). • Pluripotent stem cells divide, forming committed stem cells, which divide and eventually mature into red cells, white cells and platelets. • You need growth factors called “colony stimulating factors” for this process. Hematopoie sis Bcell T-cell Red cells Platelets Hematopoietic stem cell (self-renewing) Eosinop hil Neutrophil Monocyte Don’t memorize these specific growth factors! Just know they are necessary. Hematopoietic System Lecture Outline • Introduction • Erythrocytes Erythrocyte Maturation • The main jobs: make hemoglobin and form red blood cell with no nucleus. • 2,500,000 red cells released into blood per second! • Start with big cell and big nucleus; size of both decreases as cell matures. • Also: chromatin starts out “fine” (seethrough), and becomes progressively more condensed (dark). Nucleus Morphologic Changes in Erythropoiesis Immature -----------------------------------------------------------------> Mature Small cells, Large cells, gorgeous basophili c cytoplas Large, m violetblue nucleus Fine chromati n (see nucleoli) with red (eosinophili c) cytoplasm Small, dark blueblack nucleus coarser, then pyknotic nucleus (eventuall y extruded) Ortho- Reticulocyte Mature Basophilic Polychromatophili red cell chromatophilic Proerythroblast* c erythroblast erythroblast erythroblast Proerythroblast * mitotic Whole process takes only 7 days! Basophilic erythroblast Polychromatic erythroblast Orthochromatic erythroblast Reticulocyte * Kristine’s Mature red cell favorite cell non-mitotic Proerythroblast: Big cell, gorgeous sky-blue cytoplasm, Proerythroblast: WOW. Basophilic erythroblast: a little smaller, with more condensed chromatin and darker Polychromatic erythroblasts: even more condensed chromatin, cytoplasm grey-blue Orthochromatic erythroblast: chromatin very condensed, cytoplasm is grey-pink-lavender Orthochromatic erythroblast extruding its Reticulocytes: no nucleus, cytoplasm is still a little more lavender than mature red cell Reticulocytes (special stain) Hematopoietic System Lecture Outline • Introduction • Erythrocytes • Platelets Thrombopoiesis • Platelets come from giant (up to 100 µm) nucleated cells called megakaryocytes. • The megakaryocyte nucleus undergoes endomitosis (replicates DNA without undergoing cell division) • Up to 32 copies of normal DNA! • Multilobed nucleus • Small fragments of megakaryocyte cytoplasm bud off, forming platelets. Megakaryocyte: huge cell with large, polypoid multilobed nucleus AHHHHHHH! Hematopoietic System Lecture Outline • Introduction • Erythrocytes • Platelets • Leukocytes • Granulocytes • Agranulocytes Hematopoietic System Lecture Outline • Introduction • Erythrocytes • Platelets • Leukocytes • Granulocytes Granulocyte Maturation • 1,250,000 granulocytes (mostly neutrophils) released per second into blood! • Maturation in bone marrow takes about 2 weeks. • Cells spend a few hours in the blood, then leave and stay where needed for a few days, then die. Morphologic Changes in Granulopoiesis Immature -----------------------------------------------------------------> Mature Cytoplasm loses its basophilic color. Chromatin becomes more condensed. Specific granules increase in Myeloblast mitotic Promyelocyte Myelocyte non-mitotic Metamyelocyte Band cell Segmented neutrophil Myeloblast: high nuclear:cytoplasmic ratio. Really fine chromatin (nucleoli visible). No Promyelocyte: biggest cell of the myeloid lineup. Lots of azurophilic (primary) granules. Myelocyte: has specific granules (and a few azurophilic granules) Metamyelocyte: nucleus indented. Band cell: almost a mature neutrophil – just doesn’t have a segmented nucleus Neutrophil: segmented nucleus (3-5 lobes) Hematopoietic System Lecture Outline • Introduction • Erythrocytes • Platelets • Leukocytes • Granulocytes • Agranulocytes Lymphopoiesis • B lymphocytes develop in the bone marrow. • T lymphocytes develop in the thymus. • B and T cells then leave and populate secondary lymphoid organs (lymph nodes, spleen). • We’ll discuss these later in a different lecture. Hematopoietic System Lecture Outline • Introduction • Erythrocytes • Platelets • Leukocytes • Granulocytes • Agranulocytes