The Circulatory System: Blood(Chapter 18)

Lecture # 2Blood (part -1)

Neutrophils

- GranulocytesLeukocytes (White blood cells, WBCs)

EosinophilsBasophils

- AgranulocytesLymphocytesMonocytes

LeukocytesThe leucocytes are the least abundant formed elements (5,000 to 10,000 WBCs/m L).

They differ from erythrocytes in that they retain their organelles throughout life. The general function of the leukocytes is protection against infectious microorganisms and other pathogens.

Granulocytes

Neutrophils

Eosinophils

Basophils

The most abundant (60-70% of circulating leukocytes).

They are about 2% to 4% of the circulating leukocytes.

Abundant, very coarse, dark violet specific granules, which take up histological stains at basic pH.

Nucleus largely hidden by the granules

They have specific granules, which contain enzymes and other chemicals employed in defense against pathogens.

Reddish to violet specific granules, which take up histological stains at pH 7.

Nucleus with 3 to 5 lobules connected by slender nuclear strands (polymorphonuclear leukocytes).

Nucleus with 2 lobules connected by a thin strand.Coarse rosy to orange-colored specific granules, which take up histological stains at acidic pH.

They are the rarest of the WBCs (less than 0.5% to 1% of the WBC count).

Functions:

1- Phagocytosis of bacteria.2- They release antimicrobial chemicals.The neutrophil count rises in response to bacterial infection (neutrophilia).

Neutrophils

Eosinophils1-Phagocytosis of antigen-antibody. complexes, allergens, and inflammatory chemicals.2- They release enzymes to destroy large parasites.

They increase in parasitic infections and allergies.

Basophils 1- They secrete histamine (vasodilator), which speeds flow of blood to an injured area2- They secrete heparin (anticoagulant), which promotes the mobility of other WBCs in the area

Granulocytes

Agranulocytes

They are second to neutrophils in abundance (25% to 33%).

They are the smallest WBCs (5 to 17 mm in diameter).

Round, ovoid or slightly dimpled nucleus, which stains dark violet and fills nearly the entire cell in small lymphocytes.

There are several classes of lymphocytes with different immune functions, but they look alike through the light microscope. (B lymphocytes, T lymphocytes, and NK lymphocytes)They are the largest WBCs, often two or three times the diameter of an RBC.

They are about 3% to 8% of WBC count.

Large and medium lymphocytes are usually seen in connective tissues. Small lymphocytes are the most common circulating lymphocytes.

The nucleus is large and clearly visible, often light violet. It is typically ovoid, kidney-shaped, or horseshoe-shaped.

The cytoplasm contains fine granules.

Lymphocytes

Monocytes

They also contains granules but they are nonspecific granules (lysosomes containing enzymes).

Lymphocytes

Monocytes

Functions:

2-They “present” antigens to activate other immune cells.

They leave bloodstream and transform into macrophages, which:

1-They destroy cells (cancer, foreign, and cells infected by viruses).

5- They provide immune memory.

4- They produce and secrete antibodies.

3- They coordinate actions of other immune cells.

2-“Present” antigens to activate other immune cells - antigen presenting cells (APCs).

1-Phagocytize pathogens and debris.

Agranulocytes

The production of WBCs is called leukopoiesis.

The production of WBCs is called leukopoiesis.

Leukopoiesis begins in the bone marrow with the same pluripotent stem cells as erythropoiesis.

EosinophilicCFUs

BasophilicCFUs

NeutrophilicCFUs

MonocyticCFUs

LymphocyticCFUs

Eosinophilicmyeloblast

Basophilicmyeloblast

Neutrophilicmyeloblast

Myeloblasts

Monoblast

Lymphoblast

Immature T-lymphocytes migrate to the thymus to complete their development.

EosinophilicCFU

BasophilicCFU

NeutrophilicCFU

MonocyticCFU

LymphocyticCFU

Eosinophilicmyeloblast

Basophilicmyeloblast

Neutrophilicmyeloblast

Myeloblasts

Monoblast

Lymphoblast

Eosinophilicmyelocyte

Basophilicmyelocyte

Neutrophilicmyelocyte

Eosinophilicpromyelocyte

Basophilicpromyelocyte

Neutrophilicpromyelocyte

Promonocyte

NK prolymphocyte, B prolymphocyte, T prolymphocyte

Colony Stimulating

Factors

They have receptors for Colony

Stimulating Factors

Mature lymphocytes and macrophages secret several types of Colony Stimulating Factors in response to infections and other immune challenges.

Colony Stimulating Factors determine what type of leukocytes will be produced in response to infections and other immune challenges.

Parasites, allergy

Eosinophilic CFUs

Eosinophilic CFUs

Basophilic CFUs

Neutrophilic CFUs

Monocytic CFUs

Lymphocytic CFUs

Colony Stimulating

Factors

Bacterial infection

Neutrophilic CFUs

Colony Stimulating

Factors

ErythropoiesisPluripotentstem cell

Colony-formingunit (CFU) Erythroblast Reticulocyte Erythrocyte

Pluripotentstem cell

Colony-forming

unit (CFU)Neutrophilic,Eosinophilic, Basophilic

Myoblasts Promyelocytes Myelocytes

Pluripotentstem cell

Colony-forming

unit (CFU)LymphocyticMonocytic

LymphoblastsMonoblasts

Prolymphocytes Promonocytes

Mature cells

Mature cells

Mature cells

Leukopoiesis

Normal (a) and Leukemic (b) Blood

Platelets

Neutrophils

Lymphocyte

Erythrocytes

(a)

Monocyte

(b) 75 µm

Leukocyte Life CycleThe red bone marrow stores and releases granulocytes and monocytes.

Circulating White Blood Cells do not stay in bloodstream.

Granulocytes circulate for 4 to 8 hours. And then migrate into the tissues, where they live 4 or 5 days.

Monocytes travel in the blood for 10 to 20 hours, then migrate into the tissues and transform in macrophages, which can live as long as a few years.

Macrophages Phagocytizing Bacteria

After maturation, most of the lymphocytes move into lymph nodes, the spleen and other lymphoid tissues

Immature lymphocytes are produced in the bone marrow.

B lymphocytes mature the bone marrow.

Lymphocytes can survive from a few weeks to decades. They leave the blood stream for the tissues and eventually enter the lymphatic system, which enter them back into the bloodstream.

T lymphocytes mature in the thymus.

The Circulatory System: Blood(Chapter 18)

Lecture # 2Blood (part -2)

Platelet Form and Function

Pseudopod

Lysosome

Open canalicular system

Mitochondrion

Granule

Platelets are not cells but small fragments of marrow cells called megacaryocytes.They are the second most abundant formed elements, after erythrocytes. Normal count from 130,000 to 400,000

They have a complex internal structure that includes lysosomes, mitochondria, microtubules, microfilaments, granules filled with platelet secretions and a system of channels called open canalicular system. They have no nucleus. When activated they emit pseudopods and can move.

Functions of Platelets1- They secret vasoconstrictors that stimulate spasmodic constriction of blood vessels and thus help reduce blood loss.

3- They secrete procoagulants or clotting factors, which promote clotting.

4- They initiate formation of clot-dissolving enzyme that dissolves blood clots that are not useful.

2- They stick together to form temporary platelet plugs to seal small breaks.

5- They secret chemicals that attract neutrophils and monocytes to sites of inflammation.

6- They internalize and destroy bacteria.

7- They secrete growth factors that stimulate mitosis to repair blood vessels.

Bloodflow

Endothelium

Sinusoid ofbone marrow

Platelet ProductionProduction of platelets is called thrombopoiesis and takes place in the bone marrow.

Eryt

hrop

oiet

in

Thrombopoietin

Megakaryocytes are gigantic cells (150 mm), visible to the naked eye, with a huge multilobular nucleus and multiple sets of chromosomes.

Proplatelets

Platelets

Duplication of DNA several times without cytoplasmic division

Megakaryocyte

Colony Stimulating

Factors

Hemostasis

It is produced by:

-Pain receptors (some directly innervate blood vessels to constrict)

- Smooth muscle injury- Platelets release serotonin (vasoconstrictor)

It is the prompt constriction of a broken vessel.

The most immediate protection against blood loss is the vascular spasm.

a) Vascular spasm:

Vascular spasm provides time for other two clotting pathways.

There are three hemostatic mechanisms: 1- Vascular spasm. 2- Platelet plug formation, and 3- Blood clotting (coagulation)

Platelets do not adhere to the endothelium because it is smooth, and is coated with prostacyclin, a platelet repellant.

Broken vessel exposes collagen.

Upon contact with collagen, platelet emit pseudopods that stick to damaged vessel and other platelets

Platelets degranulate releasing a variety of substances that attract more platelets, promote platelet aggregation and produce vasoconstriction.

b) Platelet plug formation

Pseudopods contract and draw walls of vessel together forming a platelet plug.

STIMULUS

Clotting occurs as platelets adhere to site

and release chemicals.

Clotting proceeds; newly forming clot grows.

Break or tear in blood vessel wall.

Released chemicalsattract more platelets, which release more chemicals.

Released chemicalsattract more platelets, which release more chemicals.

Feedback cycle initiated

Feedback cycle ends after clot seals break.

Positive feedback mechanism

It is the last but the most effective defense against bleeding.

c) Coagulation (blood clotting)

The final goal of coagulation is to transform the fibrinogen (a soluble protein) into fibrin, a sticky protein that adheres to the blood vessels and form a net where blood cells are trapped.

Fibrinogen Fibrin

Prothrombin Thrombin

The enzyme thrombin transforms the soluble fibrinogen into short strands of fibrin. But before, prothrombin has to be activated to active thrombin.

Factor XIII

Factor XIII cross-links the fibrin strands to create a dense aggregation called fibrin polymer, which is the structural framework of the blood clot.

Fibrinpolymer

Prothrombin Thrombin

Damaged tissue Platelets

Thromboplastin (factor III)

Hageman factor (factor XII)

Extrinsic Mechanism Intrinsic Mechanism

Ca+2 Ca+2

Inactive Factor X

Prothrombin activator

Active Factor X

The activation cascade to factor X is longer.

The activation cascade to factor X is shorter.

Fibrinogen Fibrin

Fibrinpolymer

The Two Mechanisms

of Coagulation

Factor XIII

It is initiated by release of tissue thromboplastin (factor III) from damaged tissue.The activation cascade to factor X is shorter.

Extrinsic Mechanism

Intrinsic Mechanism

It is initiated by platelets releasing Hageman factor (factor XII ).The activation cascade to factor X is longer.

Calcium is required for either pathway.In most cases of bleeding, both the extrinsic and extrinsic mechanism work simultaneously.