BLOOD and HEMOPOIESIS

Assoc. Prof. Dr. Karim Al-Jashamy IMS/MSU 2010

Formed Elements of Blood

Erythrocytes (RBC) Leukocytes (WBC)
Granulocytes Agranulocytes

Platelets (Thrombocytes) Blood smear, stain using Wright. Aspirate bone (sternum, iliac crest) for bone marrow smear.

Functions of Blood
Transport of:
Gases, nutrients, waste products Processed molecules Regulatory molecules

Regulation of pH and osmosis Maintenance of body temperature Protection against foreign substances Clot formation
19-3

Composition of Blood

Plasma
Liquid part of blood
Pale yellow made up of 91% water, 9% other

Colloid: Liquid containing suspended substances that dont settle out

Albumin: Important in regulation of water movement between tissues and blood Globulins: Immune system or transport molecules Fibrinogen: Responsible for formation of blood clots
19-5

Formed Elements
Red blood cells (erythrocytes) White blood cells (leukocytes)
Granulocytes
Neutrophils Eosinophils Basophils

Agranulocytes
Lymphocytes Monocytes

Platelets (thrombocytes)
19-6

Production of Formed Elements

Hematopoiesis or hemopoiesis: Process of blood cell production Stem cells: All formed elements derived from single population
Proerythroblasts: Develop into red blood cells Myeloblasts: Develop into basophils, neutrophils, eosinophils Lymphoblasts: Develop into lymphocytes Monoblasts: Develop into monocytes Megakaryoblasts: Develop into platelets
19-7

Erythrocytes
Structure
Biconcave, anucleate

Components
Hemoglobin Lipids, ATP, carbonic anhydrase

Function
Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs
19-8

ERYTHROCYTE
Numerous (5 x 106) / ml. Mature cell has no nucleus, organelles. Transports O2 and CO2.

SEM RBC

RBC
Biconcave shape increases surface area 20-30%. Readily deform and pass through capillaries. Cytoskeleton is unique. Spectrin is major protein. Hemoglobin.

Energy from anaerobic respiration of glucose. (No mitochondria present)

Lifespan is 120 days. Removed by spleen and liver.

19-10

TEM RBC

Reticulocyte with a few organelles.

RBC in capillary

19-11

Hemoglobin
Hemoglobin (haemoglobin and abbreviated Hb or Hgb) is the ironcontaining oxygen-tran also spelled sport metalloprotein in the red blood cells of vertebrates. In mammals, the protein makes up about 97% of the red blood cell's dry content, and around 35% of the total content (including water). Hemoglobin has an oxygen binding capacity of between 1.36 and 1.37 ml O2 per gram of hemoglobin, which increases the total blood oxygen capacity seventyfold.

19-12

 Hemoglobin is also found in outside red blood cells and

their progenitor lines. Other cells that contain hemoglobin include

dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, and mesangial cells in the kidney.
In these tissues, hemoglobin has a non-oxygen carrying function as an antioxidant and a regulator of iron metabolism. 19-13

Hemoglobin

Consists of: 4 globin molecules: Transport carbon dioxide (carbonic anhydrase involved), nitric oxide 4 heme molecules: Transport oxygen
Iron is required for oxygen transport

Normal values
Hemoglobin is measured in grams per deciliter of blood. The normal levels are 1.5-3 years - 12.5 Birth - 172 1 day - 192 2-6 d - 192.5 14-23 d - 15.51 24-37 d - 142 40-50 d - 132 2-2.5 month- 11.51 3-3.5 m - 111 5-7 m - 11.51 8-10 m - 11.7.5 11-13.5 m - 12.5

5 y - 12.71 10 y - 13.21 Men - 15.51 Women - 13.7 Pregnant women: 11 to 12 g/dl

Women: 12.1 to 15.1 g/dl Men: 13.8 to 17.2 g/dl Children: 11 to 16 g/dl Pregnant women: 11 to 12 g/dl
19-15

Erythropoiesis

Production of red blood cells

Stem cells proerythroblasts early erythroblasts intermediate late reticulocytes

Erythropoietin: Hormone to stimulate RBC production

19-16

Hematopoiesis

19-17

Hemoglobin Breakdown

19-18

Leukocytes

19-19

Leukocytes
Protect body against microorganisms and remove dead cells and debris Movements
Ameboid Diapedesis Chemotaxis Passive Immunity Active Immunity Antigen Antibody

Diapedesis: The movement or passage of blood cells, especially white blood cells,
through intact capillary walls into surrounding body tissue

 Types
Neutrophils: Most common; phagocytic cells destroy bacteria (60%) Eosinophils: Detoxify chemicals; reduce inflammation (4%) Basophils: Alergic reactions; Release histamine, heparin increase inflam. response (1%) Lymphocytes: Immunity 2 types; b & t Cell types. IgG-infection, IgM-microbes, IgA-Resp & GI, IgEAlergy, IgD-immune response Monocytes: Become macrophages 19-21

NEUTROPHIL

Neutrophils, mature and almost!

Neutrophil Characteristics
60-70% of leukocytes diameter 10-12 m nucleus 2-8 lobes

chromatin in dense coarse lumps 'drumstick' on lobe in 3% of neutrophils in females (Barr body)

Neutrophils

Mature and younger Cells (lobes)

Movement by pseudopodia. Engulfed bacterium.

Neutrophils (Polymorphs)
Produced in bone marrow. Granulocyte. Highly motile, phagocytic. Acute inflammatory response to tissue injury; ingest, destroy damaged tissue & bacteria. Lifetime activity consists of one burst of phagocytosis!

TEM Neutrophil
5 lobed nucleus. Primary granules are lysosomes. Secondary granules (secretory) contain substances for inflammatory processes (complement activation, leucocyte adhesion, bacterial cell wall lysis). Few other organelles (mitochondria). Glycogen for glycolysis in O2depleted areas.

LYMPHOCYTE

Lymphocyte Characteristics
20-25% of leukocytes

Diameter 6-8 m.
Nucleus spheroid or ovoid. Chromatin in dense lumps.

Cytoplasm scarce and stained pale blue

Functions of Lymphocyte
Central role in immunological defense. Most in circulating blood are inactive. Large lymphocytes (9-15m) are active B cells en route to tissues where they become plasma cells. T lymphocytes form in red marrow and move to thymus.

Lymphocytes

Large (activated) and small (inactive) lymphocytes.

Lymphocyte
A few mitochondria and other organelles are present.

MONOCYTE

Monocyte Characteristics
3-8% of leukocytes. Largest leukocyte (20 m). Nucleus indented and pale. Cytoplasm abundant and basophilic, nonuniform (foamy) appearance. Cytoplasm may contain a few fine azurophilic granules.

Functions of Monocytes
Migrate to tissues and become microphages. Respond to necrotic material, invading microorganisms, and inflammation. Large content of hydrolytic enzymes. Great capacity for phagocytosis! Concept of a single functional unit, the monocytemacrophage system consisting of Kupffer cells of liver, microglia of CNS, osteoclasts.

Monocytes

Mature cell has greater Indentation of nucleus.

SEM Monocyte
Granules are similar to lysosomes (acid phosphatase, peroxidase). Numerous golgi, mitochondria, ribosomes.

BASOPHIL

Basophil Characteristics
Less than 1% of leukocytes. Diameter 14 m. Forms in red bone marrow. Nucleus large and bilobed. Chromatin is more finely textured so nucleus is more pale staining. Cytoplasm filled with large dark-blue staining granules (basophilic) which may obscure nucleus (blackberry appearance).

Basophil
Function: immunological response to parasites. Contain many mediators of inflammatory response. Closely related to mast cells. Basophils and mast cells bind to IgE produced in response to allergens. Triggers rapid exocytosis of granule contents (degranulation). This is the cause of immediate hypersensitivity reaction characteristic of allergic rhinitis, some forms of asthma, urticaria, anaphylactic shock).

Basophil

Bilobed nucleus Granules (S) contain heparin, leukotrienes, histamine. Mitochondria, ribosomes, glycogen in cytoplasm.

EOSINOPHIL

Eosinophil Characteristics
Up to 5% of leukocytes. Diameter 12-15 m. Nucleus usually bilobed. Chromatin clumped but not as dense as in neutrophil. Cytoplasm filled with numerous large eosinophilic (acidophilic) granules which stain pale-pink.

Functions of Eosinophils
Phagocytic for antigen-antibody complexes. Defense against parasites. Release granules against parasites which are injured by enzymes. Undergo chemotaxis in response to bacteria but preferentially respond to basophils and mast cells.

SEM Eosinophil
Specific granules (S) stains reddish. S granules contain many hydrolytic enzymes. Contains glycogen, some mitochondria, rER, sER.

Thrombocytes
Cell fragments pinched off from megakaryocytes in red bone marrow Important in preventing blood loss
Platelet plugs Promoting formation and contraction of clots

19-46

Hemostasis
Arrest of bleeding Events preventing excessive blood loss
Vascular spasm: Vasoconstriction of damaged blood vessels Platelet plug formation Coagulation or blood clotting

19-47

Platelets

Very complex with organelles but no nuclei. Function: form plugs in damaged vessels, promote clot formation, secrete substances that are involved in repair of vessels.

Platelet Plug Formation

19-49

Coagulation
Stages
Activation of prothrombinase Conversion of prothrombin to thrombin Conversion of fibrinogen to fibrin

Pathways
Extrinsic Intrinsic
19-50

Clot Formation

19-51

Fibrinolysis

Clot dissolved by activity of plasmin, an enzyme which hydrolyzes fibrin

19-52

Blood Grouping
Determined by antigens (agglutinogens) on surface of RBCs Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs Groups
ABO and Rh
19-53

ABO Blood Groups

19-54

Agglutination Reaction

19-55

Rh Blood Group
First studied in rhesus monkeys Types
Rh positive: Have these antigens present on surface of RBCs Rh negative: Do not have these antigens present

Hemolytic disease of the newborn (HDN)

Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs
19-56

Erythroblastosis Fetalis

19-57

Diagnostic Blood Tests

Type and crossmatch Complete blood count
Red blood count Hemoglobin measurement Hematocrit measurement

White blood count Differential white blood count Clotting

19-58

Blood Disorders
Erythrocytosis: RBC overabundance Anemia: Deficiency of hemoglobin
Iron-deficiency Pernicious Hemorrhagic Hemolytic Sickle-cell

Hemophilia Thrombocytopenia Leukemia Septicemia Malaria Infectious mononucleosis Hepatitis

19-59