The Circulatory System Blood Chapter 18 Lecture 2

The Circulatory System: Blood (Chapter 18) Lecture # 2 Blood (part -1)

Leukocytes The 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 - Agranulocytes Lymphocytes Monocytes Leukocytes (White blood cells, WBCs)

Granulocytes They have specific granules, which contain enzymes and other chemicals employed in defense against pathogens. The most abundant (60 -70% of circulating leukocytes). Nucleus with 3 to 5 lobules connected by slender nuclear strands (polymorphonuclear leukocytes). Neutrophils Eosinophils Reddish to violet specific granules, which take up histological stains at p. H 7. They are about 2% to 4% of the circulating leukocytes. Nucleus with 2 lobules connected by a thin strand. Coarse rosy to orange-colored specific granules, which take up histological stains at acidic p. H. They are the rarest of the WBCs (less than 0. 5% to 1% of the WBC count). Nucleus largely hidden by the granules Basophils Abundant, very coarse, dark violet specific granules, which take up histological stains at basic p. H.

Granulocytes Neutrophils Functions: 1 - Phagocytosis of bacteria. 2 - They release antimicrobial chemicals. The neutrophil count rises in response to bacterial infection (neutrophilia). Eosinophils 1 -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 area 2 - They secrete heparin (anticoagulant), which promotes the mobility of other WBCs in the area

Agranulocytes They also contains granules but they are nonspecific granules (lysosomes containing enzymes). They are second to neutrophils in abundance (25% to 33%). They are the smallest WBCs (5 to 17 mm in diameter). Large and medium lymphocytes are usually seen in connective tissues. Small lymphocytes are the most common circulating lymphocytes. Lymphocytes 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. The nucleus is large and clearly visible, often light violet. It is typically ovoid, kidney-shaped, or horseshoe-shaped. The cytoplasm contains fine granules. Monocytes

Agranulocytes Lymphocytes Functions: 1 -They destroy cells (cancer, foreign, and cells infected by viruses). 2 -They “present” antigens to activate other immune cells. 3 - They coordinate actions of other immune cells. 4 - They produce and secrete antibodies. 5 - They provide immune memory. Monocytes They leave bloodstream and transform into macrophages, which: 1 -Phagocytize pathogens and debris. 2 -“Present” antigens to activate other immune cells - antigen presenting cells (APCs).

The production of WBCs is called leukopoiesis.

The production of WBCs is called leukopoiesis. Eosinophilic CFUs Myeloblasts Eosinophilic myeloblast Basophilic CFUs Neutrophilic myeloblast Monocytic CFUs Leukopoiesis begins in the bone marrow with the same pluripotent stem cells as erythropoiesis. Lymphoblast Lymphocytic CFUs Immature T-lymphocytes migrate to the thymus to complete their development.

Eosinophilic myeloblast Eosinophilic promyelocyte Eosinophilic myelocyte Basophilic CFU Basophilic myeloblast Basophilic promyelocyte Basophilic myelocyte Neutrophilic CFU Neutrophilic myeloblast Neutrophilic promyelocyte Neutrophilic myelocyte Eosinophilic CFU Myeloblasts Monoblast Monocytic CFU Promonocyte Lymphoblast Lymphocytic CFU NK prolymphocyte, B prolymphocyte, T prolymphocyte

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. Eosinophilic CFUs Basophilic CFUs Neutrophilic CFUs Monocytic CFUs They have receptors for Colony Stimulating Factors Lymphocytic CFUs Bacterial infection Parasites, allergy Colony Stimulating Factors Eosinophilic CFUs Colony Stimulating Factors Neutrophilic CFUs

Erythropoiesis Pluripotent stem cell Colony-forming unit (CFU) Erythroblast Reticulocyte Erythrocyte Mature cells Leukopoiesis Pluripotent stem cell Colonyforming unit (CFU) Neutrophilic, Eosinophilic, Basophilic Pluripotent stem cell Colonyforming unit (CFU) Lymphocytic Monocytic Myoblasts Myelocytes Mature cells Prolymphocytes Promonocytes Mature cells Promyelocytes Lymphoblasts Monoblasts

Platelets Monocyte Neutrophils Lymphocyte Erythrocytes (a) (b) 75 µm Normal (a) and Leukemic (b) Blood

Leukocyte Life Cycle The 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

Immature lymphocytes are produced in the bone marrow. B lymphocytes mature the bone marrow. T lymphocytes mature in the thymus. After maturation, most of the lymphocytes move into lymph nodes, the spleen and other lymphoid tissues 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.

The Circulatory System: Blood (Chapter 18) Lecture # 2 Blood (part -2)

Platelet Form and Function 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 Pseudopod Lysosome Open canalicular system Mitochondrion Granule 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 Platelets 1 - They secret vasoconstrictors that stimulate spasmodic constriction of blood vessels and thus help reduce blood loss. 2 - They stick together to form temporary platelet plugs to seal small breaks. 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. 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.

Colony Stimulating Factors Platelet Production Ery th rop oie tin Production of platelets is called thrombopoiesis and takes place in the bone marrow. Megakaryocytes are gigantic cells (150 mm), visible to the naked eye, with a huge multilobular nucleus and multiple sets of chromosomes. Platelets Bloodflow Proplatelets Endothelium in oiet bop m Thro Sinusoid of bone marrow Duplication of DNA several times without cytoplasmic division Megakaryocyte

Hemostasis There are three hemostatic mechanisms: 1 - Vascular spasm. 2 - Platelet plug formation, and 3 - Blood clotting (coagulation) The most immediate protection against blood loss is the vascular spasm. a) Vascular spasm: It is the prompt constriction of a broken vessel. Vascular spasm provides time for other two clotting pathways. It is produced by: -Pain receptors (some directly innervate blood vessels to constrict) - Smooth muscle injury - Platelets release serotonin (vasoconstrictor)

b) Platelet plug formation 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 Pseudopods contract and draw walls of vessel together forming a platelet plug. Platelets degranulate releasing a variety of substances that attract more platelets, promote platelet aggregation and produce vasoconstriction.

Positive feedback mechanism STIMULUS Break or tear in blood vessel wall. Feedback cycle initiated Feedback cycle ends after clot seals break. Clotting occurs as platelets adhere to site and release chemicals. Released chemicals attract more platelets, which release more chemicals. Clotting proceeds; newly forming clot grows. Released chemicals attract more platelets, which release more chemicals.

c) Coagulation (blood clotting) It is the last but the most effective defense against bleeding.

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. The enzyme thrombin transforms the soluble fibrinogen into short strands of fibrin. But before, prothrombin has to be activated to active thrombin. Factor XIII cross-links the fibrin strands to create a dense aggregation called fibrin polymer, which is the structural framework of the blood clot. Prothrombin Fibrinogen Thrombin Factor XIII Fibrin polymer

Extrinsic Mechanism Intrinsic Mechanism Damaged tissue Thromboplastin (factor III) The activation cascade to factor X is shorter. Platelets Ca+2 Inactive Factor X The Two Mechanisms of Coagulation Hageman factor (factor XII) The activation cascade to factor X is longer. Factor XIII Active Factor X Prothrombin activator Prothrombin Fibrinogen Fibrin Thrombin Fibrin polymer

Extrinsic Mechanism It is initiated by release of tissue thromboplastin (factor III) from damaged tissue. The activation cascade to factor X is shorter. Intrinsic Mechanism It is initiated by platelets releasing Hageman factor (factor XII ). The activation cascade to factor X is longer. Calcium is required either pathway. for In most cases of bleeding, both the extrinsic and extrinsic mechanism work simultaneously.