17 Blood: Modified by Dr. Par Mohammadian

Blood Composition Blood Fluid connective tissue Plasma – non-living fluid matrix Formed elements – living blood "cells" suspended in plasma Erythrocytes (red blood cells, or RBCs) Leukocytes (white blood cells, or WBCs) Platelets © 2013 Pearson Education, Inc.

Spun tube of blood yields three layers Blood Composition Spun tube of blood yields three layers Plasma on top (~55%) Erythrocytes on bottom (~45%) WBCs and platelets in Buffy coat (< 1%) Hematocrit Percent of blood volume that is RBCs 47% ± 5% for males; 42% ± 5% for females © 2013 Pearson Education, Inc.

Figure 17.1 The major components of whole blood. Slide 1 Formed elements Plasma • 55% of whole blood • Least dense component Buffy coat • Leukocytes and platelets • <1% of whole blood Erythrocytes Withdraw blood and place in tube. 1 Centrifuge the blood sample. 2 • 45% of whole blood (hematocrit) • Most dense component © 2013 Pearson Education, Inc.

Physical Characteristics and Volume Sticky, opaque fluid with metallic taste Color varies with O2 content High O2 - scarlet; Low O2 - dark red pH 7.35–7.45 ~8% of body weight Average volume 5–6 L for males; 4–5 L for females © 2013 Pearson Education, Inc.

Functions of Blood Distribution Functions Functions include Distributing substances Regulating blood levels of substances Protection Distribution Functions Delivering O2 and nutrients to body cells Transporting metabolic wastes to lungs and kidneys for elimination Transporting hormones from endocrine organs to target organs

Maintaining body temperature by absorbing and distributing heat Regulation Functions Maintaining body temperature by absorbing and distributing heat Maintaining normal pH using buffers; alkaline reserve of bicarbonate ions Maintaining adequate fluid volume in circulatory system © 2013 Pearson Education, Inc.

Protection Functions Preventing blood loss Preventing infection Plasma proteins and platelets initiate clot formation Preventing infection Antibodies Complement proteins WBCs © 2013 Pearson Education, Inc.

Over 100 dissolved solutes Blood Plasma 90% water Over 100 dissolved solutes Nutrients, gases, hormones, wastes, proteins, inorganic ions Plasma proteins most abundant solutes Remain in blood; not taken up by cells Proteins produced mostly by liver 60% albumin; 36% globulins; 4% fibrinogen © 2013 Pearson Education, Inc.

Table 17.1 Composition of Plasma (1 of 2) © 2013 Pearson Education, Inc.

Table 17.1 Composition of Plasma (2 of 2) © 2013 Pearson Education, Inc.

Albumin 60% of plasma protein Functions Substance carrier Blood buffer Major contributor of plasma osmotic pressure © 2013 Pearson Education, Inc.

Only WBCs are complete cells RBCs have no nuclei or other organelles Formed Elements Only WBCs are complete cells RBCs have no nuclei or other organelles Platelets are cell fragments Most formed elements survive in bloodstream only few days Most blood cells originate in bone marrow and do not divide © 2013 Pearson Education, Inc.

Platelets Erythrocytes Monocyte Neutrophils Lymphocyte

Biconcave discs, anucleate, essentially no organelles Erythrocytes Biconcave discs, anucleate, essentially no organelles Diameters larger than some capillaries Filled with hemoglobin (Hb) for gas transport Contain plasma membrane protein spectrin and other proteins Spectrin provides flexibility to change shape Major factor contributing to blood viscosity

Figure 17.3 Structure of erythrocytes (red blood cells). 2.5 µm Side view (cut) 7.5 µm Top view © 2013 Pearson Education, Inc.

Structural characteristics contribute to gas transport Erythrocytes Structural characteristics contribute to gas transport Biconcave shape—huge surface area relative to volume >97% hemoglobin (not counting water) No mitochondria; ATP production anaerobic; do not consume O2 they transport Superb example of complementarity of structure and function © 2013 Pearson Education, Inc.

RBCs dedicated to respiratory gas transport Erythrocyte Function RBCs dedicated to respiratory gas transport Hemoglobin binds reversibly with oxygen Normal values Males - 13–18g/100ml; Females - 12–16 g/100ml © 2013 Pearson Education, Inc.

Globin composed of 4 polypeptide chains Hemoglobin Structure Globin composed of 4 polypeptide chains Two alpha and two beta chains Heme pigment bonded to each globin chain Gives blood red color Heme's central iron atom binds one O2 Each Hb molecule can transport four O2 Each RBC contains 250 million Hb molecules © 2013 Pearson Education, Inc.

Figure 17.4 Structure of hemoglobin.  Globin chains Heme group  Globin chains Hemoglobin consists of globin (two alpha and two beta polypeptide chains) and four heme groups. Iron-containing heme pigment. © 2013 Pearson Education, Inc.

Hemoglobin (Hb) O2 loading in lungs O2 unloading in tissues Produces oxyhemoglobin (ruby red) O2 unloading in tissues Produces deoxyhemoglobin or reduced hemoglobin (dark red) CO2 loading in tissues 20% of CO2 in blood binds to Hb  carbaminohemoglobin © 2013 Pearson Education, Inc.

Blood cell formation in red bone marrow Hematopoiesis Blood cell formation in red bone marrow Composed of reticular connective tissue and blood sinusoids In adult, found in axial skeleton, girdles, and proximal epiphyses of humerus and femur © 2013 Pearson Education, Inc.

Hematopoietic stem cells (Hemocytoblasts) Hematopoiesis Hematopoietic stem cells (Hemocytoblasts) Give rise to all formed elements Hormones and growth factors push cell toward specific pathway of blood cell development Committed cells cannot change New blood cells enter blood sinusoids © 2013 Pearson Education, Inc.

Erythropoiesis: Red Blood Cell Production Stages Myeloid stem cell transformed into proerythroblast In 15 days proerythroblasts develop into basophilic, then polychromatic, then orthochromatic erythroblasts, and then into reticulocytes Reticulocytes enter bloodstream; in 2 days mature RBC © 2013 Pearson Education, Inc.

As myeloid stem cell transforms Erythropoiesis As myeloid stem cell transforms Ribosomes synthesized Hemoglobin synthesized; iron accumulates Ejection of nucleus; formation of reticulocyte (young RBC) Reticulocyte ribosomes degraded; Then become mature erythrocytes Reticulocyte count indicates rate of RBC formation © 2013 Pearson Education, Inc.

Figure 17.5 Erythropoiesis: formation of red blood cells. Stem cell Committed cell Developmental pathway Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus Hematopoietic stem cell (hemocytoblast) Basophilic erythroblast Polychromatic erythroblast Orthochromatic erythroblast Proerythroblast Reticulocyte Erythrocyte © 2013 Pearson Education, Inc.

Regulation of Erythropoiesis Too few RBCs leads to tissue hypoxia Too many RBCs increases blood viscosity > 2 million RBCs made per second Balance between RBC production and destruction depends on Hormonal controls Adequate supplies of iron, amino acids, and B vitamins © 2013 Pearson Education, Inc.

Hormonal Control of Erythropoiesis Hormone Erythropoietin (EPO) Direct stimulus for erythropoiesis Always small amount in blood to maintain basal rate High RBC or O2 levels depress production Released by kidneys (some from liver) in response to hypoxia Dialysis patients have low RBC counts © 2013 Pearson Education, Inc.

Hormonal Control of Erythropoiesis Causes of hypoxia Decreased RBC numbers due to hemorrhage or increased destruction Insufficient hemoglobin per RBC (e.g., iron deficiency) Reduced availability of O2 (e.g., high altitudes) © 2013 Pearson Education, Inc.

Hormonal Control of Erythropoiesis Effects of EPO Rapid maturation of committed marrow cells Increased circulating reticulocyte count in 1–2 days Some athletes abuse artificial EPO Dangerous consequences Testosterone enhances EPO production, resulting in higher RBC counts in males © 2013 Pearson Education, Inc.

Figure 17.6 Erythropoietin mechanism for regulating erythropoiesis. Slide 1 IMBALANCE Homeostasis: Normal blood oxygen levels Stimulus: Hypoxia (inadequate O2 delivery) due to 1 O2-carrying ability of blood rises. 5 IMBALANCE • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 Enhanced erythropoiesis increases RBC count. 4 Kidney (and liver to a smaller extent) releases erythropoietin. 2 Erythropoietin stimulates red bone marrow. 3 © 2013 Pearson Education, Inc.

Dietary Requirements for Erythropoiesis Nutrients—amino acids, lipids, and carbohydrates Iron Available from diet 65% in Hb; rest in liver, spleen, and bone marrow Free iron ions toxic Stored in cells as ferritin and hemosiderin Transported in blood bound to protein transferrin Vitamin B12 and folic acid necessary for DNA synthesis for rapidly dividing cells (developing RBCs) © 2013 Pearson Education, Inc.

Fate and Destruction of Erythrocytes Life span: 100–120 days No protein synthesis, growth, division Old RBCs become fragile; Hb begins to degenerate Get trapped in smaller circulatory channels especially in spleen Macrophages engulf dying RBCs in spleen © 2013 Pearson Education, Inc.

Fate and Destruction of Erythrocytes Heme and globin are separated Iron salvaged for reuse Heme degraded to yellow pigment bilirubin Liver secretes bilirubin (in bile) into intestines Degraded to pigment urobilinogen Pigment leaves body in feces as stercobilin Globin metabolized into amino acids Released into circulation © 2013 Pearson Education, Inc.

Figure 17.7 Life cycle of red blood cells. Slide 1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. 1 2 Erythropoietin levels rise in blood. Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow. 3 New erythrocytes enter bloodstream; function about 120 days. 4 Aged and damaged red blood cells are engulfed by macrophages of spleen, liver, and bone marrow; the hemoglobin is broken down. 5 Hemoglobin Heme Globin Bilirubin is picked up by the liver. Iron is stored as ferritin or hemosiderin. Amino acids Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis. Bilirubin is secreted into intestine in bile where it is metabolized to stercobilin by bacteria. Circulation Raw materials are made available in blood for erythrocyte synthesis. 6 Food nutrients (amino acids, Fe, B12, and folic acid) are absorbed from intestine and enter blood. Stercobilin is excreted in feces. © 2013 Pearson Education, Inc.

Make up <1% of total blood volume Leukocytes Make up <1% of total blood volume 4,800 – 10,800 WBCs/μl blood Function in defense against disease Can leave capillaries via diapedesis Move through tissue spaces by ameboid motion and positive chemotaxis Leukocytosis: WBC count over 11,000/mm3 Normal response to infection © 2013 Pearson Education, Inc.

Leukocytes: Two Categories Granulocytes – Visible cytoplasmic granules Neutrophils, eosinophils, basophils Agranulocytes – No visible cytoplasmic granules Lymphocytes, monocytes © 2013 Pearson Education, Inc.

Granulocytes Granulocytes Larger and shorter-lived than RBCs Lobed nuclei Cytoplasmic granules stain specifically with Wright's stain All phagocytic to some degree Platelets Erythrocytes Monocyte Neutrophils Lymphocyte

Second most numerous WBC Lymphocytes Second most numerous WBC Large, dark-purple, circular nuclei with thin rim of blue cytoplasm Mostly in lymphoid tissue (e.g., lymph nodes, spleen); few circulate in blood Crucial to immunity Platelets Erythrocytes Monocyte Neutrophils Lymphocyte © 2013 Pearson Education, Inc.

Lymphocytes Two types T lymphocytes (T cells) act against virus-infected cells and tumor cells B lymphocytes (B cells) give rise to plasma cells, which produce antibodies © 2013 Pearson Education, Inc.

Abundant pale-blue cytoplasm Monocytes Largest leukocytes Abundant pale-blue cytoplasm Dark purple-staining, U- or kidney-shaped nuclei Platelets Erythrocytes Monocyte Neutrophils Lymphocyte © 2013 Pearson Education, Inc.

Leave circulation, enter tissues, and differentiate into macrophages Monocytes Leave circulation, enter tissues, and differentiate into macrophages Actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections Activate lymphocytes to mount an immune response

All leukocytes originate from hemocytoblasts Leukopoiesis Production of WBCs Stimulated by 2 types of chemical messengers from red bone marrow and mature WBCs Interleukins (e.g., IL-3, IL-5) Colony-stimulating factors (CSFs) named for WBC type they stimulate (e.g., granulocyte-CSF stimulates granulocytes) All leukocytes originate from hemocytoblasts © 2013 Pearson Education, Inc.

Lymphoid stem cells  lymphocytes Myeloid stem cells  all others Leukopoiesis Lymphoid stem cells  lymphocytes Myeloid stem cells  all others Progression of all granulocytes Myeloblast  promyelocyte  myelocyte  band  mature cell Granulocytes stored in bone marrow 3 times more WBCs produced than RBCs Shorter life span; die fighting microbes © 2013 Pearson Education, Inc.

Progression of agranulocytes differs Monocytes – live several months Leukopoiesis Progression of agranulocytes differs Monocytes – live several months Share common precursor with neutrophils Monoblast  promonocyte  monocyte Lymphocytes – live few hours to decades Lymphoid stem cell  T lymphocyte precursors (travel to thymus) and B lymphocyte precursors

Figure 17.11 Leukocyte formation. Stem cells Hematopoietic stem cell (hemocytoblast) Myeloid stem cell Lymphoid stem cell Committed cells Myeloblast Myeloblast Myeloblast Monoblast B lymphocyte precursor T lymphocyte precursor Developmental pathway Promyelocyte Promyelocyte Promyelocyte Promonocyte Eosinophilic myelocyte Basophilic myelocyte Neutrophilic myelocyte Eosinophilic band cells Basophilic band cells Neutrophilic band cells Granular leukocytes Agranular leukocytes Eosinophils Basophils Neutrophils Monocytes B lymphocytes T lymphocytes (a) (b) (c) (d) (e) (f) Some become Some become Some become Macrophages (tissues) Plasma cells Effector T cells

Cytoplasmic fragments of megakaryocytes Platelets Cytoplasmic fragments of megakaryocytes Blue-staining outer region; purple granules Granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF) Act in clotting process Normal = 150,000 – 400,000 platelets /ml of blood © 2013 Pearson Education, Inc.

Form temporary platelet plug that helps seal breaks in blood vessels Platelets Form temporary platelet plug that helps seal breaks in blood vessels Circulating platelets kept inactive and mobile by nitric oxide (NO) and prostacyclin from endothelial cells lining blood vessels Age quickly; degenerate in about 10 days Formation regulated by thrombopoietin Derive from megakaryoblast Mitosis but no cytokinesis  megakaryocyte - large cell with multilobed nucleus

Figure 17.12 Formation of platelets. Stem cell Developmental pathway Hematopoietic stem cell (hemocytoblast) Megakaryoblast (stage I megakaryocyte) Megakaryocyte (stage II/III) Megakaryocyte (stage IV) Platelets © 2013 Pearson Education, Inc.

Table 17.2 Summary of Formed Elements of the Blood (1 of 2) © 2013 Pearson Education, Inc.

Table 17.2 Summary of Formed Elements of the Blood (2 of 2) © 2013 Pearson Education, Inc.