Module IB Blood & Blood Formation Histology and Embryology Martin Špaček, MD (m.spacek@centrum.cz) http://www.lf3.cuni.cz/histologie
Approximately 7% of a person's weight is blood (about 5 L) Blood consists of the formed elements and plasma
If blood is removed from the circulatory system, it will clot Serum: a yellow clear fluid lacking fibrinogen Blood clot: contains formed elements in a fibrin-containing network
Blood collected in the presence of an anticoagulant (heparin or sodium citrate) and centrifuged Plasma Buffy coat: leukocytes and plateles Red blood cells: the hematocrit 40-50% in the men 35-45% in women
Composition of Plasma Plasma is 92% water, about 1% ions and small soluble elements and 7% protein The main proteins: albumin globulins fibrinogen
Formed Elements of Blood Red blood cells (erythrocytes) White blood cells (leukocytes) granulocytes agranulocytes Platelets (thrombocytes)
Studying Blood Cells: Preparation of the Blood Smear Spread a drop of blood in a thin layer on a slide
Staining of Blood Cells After fixation, a polychromatic Romanowsky-type staining technique such as the Giemsa, Wright or Leishman method is used Four distinctive staining characteristic can be identified: basophilia (deep blue) DNA (nuclei), RNA azurophilia (purple) lysosomes eosinophilia (pink) hemoglobin in RBCs neutrophilia (salmon pink) specific granules of neutrophil leukocytes
Erythrocytes Biconcave disks Women average about 4.8 x 10 6 per µl Men average about 5.4 x 10 6 per µl Your body makes 2.5 million red blood cells every second
Erythrocytes 7.2 µm in diameter macrocytes diameter > 9 µm microcytes diameter < 6 µm
Enucleated Erythrocytes endpoint of a developmental series of nucleated precursors they are terminally differentiated live about 120 days No organelles Oxygen and carbon dioxide transport only function packed with hemoglobin
Hemoglobin Consists of four polypeptides Each of these is attached the prosthetic group heme
Hemoglobin There is one atom of iron at the center of each heme
Hemoglobin There is one atom of iron at the center of each heme One molecule of oxygen can bind to each heme
Sickle Cell Disease Inherited alteration in hemoglobin Caused by a mutation of one nucleotide in the DNA of the gene for the β chain
Sickle Cell Disease When hemoglobin S is deoxygenated, it polymerizes and forms rigid aggregates RBCs lose their normal elasticity
Sickle Cell Disease Sickle cell disease results in several complications anemia pain infections stroke
Sickle Cell Disease Survival advantage to heterozygotes in regions of endemic malaria
Thrombocytes (Platelets) Cell fragments Smallest formed elements (2-4 µm in diameter) Responsible for initial clot formation Normal values: 150,000 to 400,000 per µl
Thrombocytes (Platelets) Hyalomere peripheral transparent zone Granulomere central zone containing purple granules Open canalicular system
Thrombocytes (Platelets)
Leukocytes Granulocytes neutrophils eosinophils basophils Agranulocytes lymphocytes monocytes
Neutrophiles Multilobed nucleus (polymorphonuclear) Granules in cytoplasm lysosomes Most numerous of granulocytes (60-70%) Phagocytic (microphages)
Neutrophiles 12-15 µm in diameter
Neutrophiles
Lobulated nuclei (typically bilobed) Large granules that attract eosin stain major basic protein 2-4% of leukocytes Diameter 12-15µm Role in allergic reactions and antiparasitic functions Eosinophiles
Eosinophiles
Eosinophiles
Rarest cells of blood Basophils less than 1% of leukocytes Diameter 12-15 µm Nucleolus divided into lobes Large specific granules attract basic dyes heparin, histamine Function in immediate hypersensitivity reactions
Basophils
Basophils
Lymphocytes 20-30% of leukocytes diameter 6-18 µm almost no cytoplasm nucleolus is round, condense and inactive T cells and B cells are morphologically identical in the unstimulated or resting state
Lymphocytes
Lymphocytes
Lymphocytes Activated B cells become plasma cells Activated T cells can become helper T cells or cytotoxic T cells
Monocytes 3-8% of leukocytes Large cells (12-20 µm) Nucleolus is oval and eccentrically placed More cytoplasm than lymphocyte Monocytes leave the blood and become macrophages
Monocytes
Differential Leukocytes Count Neutrophil 60-70% Eosinophil 2-4% Basophil 0.5-1% Lymphocyte 20-30% Monocyte 3-8% Changes in their relative number indicate some disorder
Differential Leukocytes Count
monocyte basophil neutrophil monocyte lymphocyte eosinophil
Hematopoiesis Prenatal formation of blood cells: commences in the yolk sac later, the liver and spleen become dominant sites of hematopoiesis from the 5 th month occurs in bone marrow
Hematopoiesis
Red Bone Marrow Hemopoietic cells surround the vascular sinusoids and are supported by reticular connective tissue
Hematopoiesis All the various types of blood cells arise from a single type of cell called a pluripotential stem cell
Hematopoiesis Stem cells proliferate and develop into either lymhoid multipotential cells or myeloid multipotential cells
Maturation of Erythrocytes Erythropoietin glycoprotein produced in the kidneys, enhances the production of RBCs Proerythroblast the first identifiable stage of erythropoiesis large, basophilic cell, which contains a large, lightly stained nulceus
Maturation of Erythrocytes Basophilic erythroblast strongly basophilic cytoplasm large number of polyribosomes involved in the synthesis of hemoglobin Polychromatophilic erythroblas Orthochromatic erythroblast cytoplasm filled with hemoglobin
Maturation of Erythrocytes The nucleolus is finally expelled The cell enters circulation as a reticulocyte, which still contains some organelles
Origin of Platelets Fragmentation of the cytoplasm of megakaryocytes Megakaryocytes are very large cells (up to 160 µm) contain large, irregularly lobulated nuclei
Maturation of Granulocytes Accumulation of nonspecific and specific granules Changes in nuclear morphology
Maturation of Monocytes Monoblast morphologically identical to the myeloblast Promonocyte large cell with basophilic cytoplasm Monocytes enter the bloodstream and then the connective tissues, where they mature into macrophages
Maturation of Lymphocytes All lymphocyte progenitor cells originate in the bone marrow
Hematopoiesis is controlled by appropriate cytokines and hormones