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

Composition of

Blood

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