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BLOOD andHEMOPOIESIS
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.
19-3
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
19-5
Plasma
• Liquid part of blood
– Pale yellow made up of 91% water, 9% other
• Colloid: Liquid containing suspended substances that don’t 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
19-6
Formed Elements
• Red blood cells (erythrocytes)
• White blood cells (leukocytes)
– Granulocytes
• Neutrophils
• Eosinophils
• Basophils
– Agranulocytes
• Lymphocytes
• Monocytes
• Platelets (thrombocytes)
19-7
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
19-8
Erythrocytes
• Structure
– Biconcave, anucleate
• Components
– Hemoglobin
– Lipids, ATP, carbonic
anhydrase
• Function
– Transport oxygen from
lungs to tissues and
carbon dioxide from
tissues to lungs
ERYTHROCYTE
• Numerous (5 x 106) /
ml.
• Mature cell has no
nucleus, organelles.
• Transports O2 and
CO2.
SEM RBC
19-10
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.
RBC
19-11
TEM RBC
Reticulocyte with a
few organelles.
RBC in capillary
19-12
Hemoglobin (haemoglobin and abbreviated Hb or Hgb) is the iron-
containing 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.
Hemoglobin
19-13
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.
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
19-15
Birth - 17±2
1 day - 19±2
2-6 d - 19±2.5
14-23 d - 15.5±1
24-37 d - 14±2
40-50 d - 13±2
2-2.5 month- 11.5±1
3-3.5 m - 11±1
5-7 m - 11.5±1
8-10 m - 11.7±.5
11-13.5 m - 12±.5
Normal values
1.5-3 years - 12±.5
5 y - 12.7±1
10 y - 13.2±1
Men - 15.5±1
Women - 13.7
Pregnant women: 11 to 12
g/dl
Hemoglobin is measured in grams per deciliter of blood. The normal
levels are
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
19-16
Erythropoiesis
• Production of red blood cells
– Stem cells proerythroblasts early erythroblasts
intermediate late reticulocytes
• Erythropoietin: Hormone to stimulate RBC production
19-17
Hematopoiesis
19-18
Hemoglobin Breakdown
19-19
Leukocytes
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
19-21
• 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, IgE-
Alergy, IgD-immune response
– Monocytes: Become macrophages
NEUTROPHIL
Neutrophils, mature and almost!
Neutrophil Characteristics
• 60-70% of leukocytes
• diameter 10-12 µm
• 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 (comple-
ment activation, leucocyte
adhesion,
bacterial cell wall lysis).
Few other organelles
(mitochondria).
Glycogen for glycolysis in O2-
depleted areas.
LYMPHOCYTE
Lymphocyte Characteristics
• 20-25% of leukocytes
• Diameter 6-8 µm.
• 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 µm).
• Nucleus indented and pale.
• Cytoplasm abundant and basophilic, non-
uniform (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 monocyte-
macrophage 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 µm.
• 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 µm.
• 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.
19-46
Thrombocytes
• Cell fragments
pinched off from
megakaryocytes in red
bone marrow
• Important in
preventing blood loss
– Platelet plugs
– Promoting formation
and contraction of clots
19-47
Hemostasis
• Arrest of bleeding
• Events preventing excessive blood loss
– Vascular spasm: Vasoconstriction of damaged
blood vessels
– Platelet plug formation
– Coagulation or blood clotting
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.
19-49
Platelet Plug Formation
19-50
Coagulation
• Stages
– Activation of
prothrombinase
– Conversion of
prothrombin to
thrombin
– Conversion of
fibrinogen to fibrin
• Pathways
– Extrinsic
– Intrinsic
19-51
Clot Formation
19-52
Fibrinolysis
• Clot dissolved by
activity of plasmin,
an enzyme which
hydrolyzes fibrin
19-53
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
19-54
ABO Blood Groups
19-55
Agglutination Reaction
19-56
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
19-57
Erythroblastosis Fetalis
19-58
Diagnostic Blood Tests
• Type and crossmatch
• Complete blood count
– Red blood count
– Hemoglobin measurement
– Hematocrit measurement
• White blood count
• Differential white blood
count
• Clotting
19-59
Blood Disorders
• Erythrocytosis: RBC
overabundance
• Anemia: Deficiency of
hemoglobin
– Iron-deficiency
– Pernicious
– Hemorrhagic
– Hemolytic
– Sickle-cell
• Hemophilia
• Thrombocytopenia
• Leukemia
• Septicemia
• Malaria
• Infectious
mononucleosis
• Hepatitis