Ch 18 Blood Pt.2

Overview of Blood

Blood is a vital fluid in the body that serves numerous functions such as the transportation of oxygen, nutrients, hormones, and waste products. It plays crucial roles in regulating body temperature, pH levels, and fluid balance, and is integral to the immune system and clotting mechanisms.

Chapter 18: Blood

Page 1: Comic Relief

A humorous segment discusses blood and the concept of a ‘Virgin Bloody Mary,’ focusing on the consumption of blood in various cultural contexts and the historical significance of blood in rituals.

Page 2: Learning Objectives

This chapter aims to explore important questions regarding pus in infected cuts, an indicator of the immune response:

• What are white blood cells (WBCs)?

• Why do they migrate to infection sites?

• Is pus composed of dead white blood cells? - These inquiries lead into the exploration of the characteristics, types, and functions of white blood cells.

White Blood Cells (Leukocytes)

Page 3: Characteristics

• Composition: White blood cells constitute less than 1% of total blood volume.

• Structure: They are full-fledged cells with nuclei and organelles, crucial for their function.

• Size: WBCs typically range from 1.5 to 3 times larger than red blood cells (RBCs).

• Function: Their essential function is to defend against pathogens through various mechanisms including phagocytosis and antibody production.

Page 4: Movement and Attraction

• Motility: Leukocytes are flexible and primarily reside in tissues rather than circulating in the bloodstream.

• Diapedesis: This refers to the process by which leukocytes pass through the walls of blood vessels to reach sites of infection.

• Chemotaxis: Leukocytes are attracted to infection sites by chemical signals released by damaged tissues and pathogens.

Page 5: Categories of Leukocytes

• Granulocytes: Characterized by visible granules in their cytoplasm when viewed under a light microscope.

• Agranulocytes: Lack visible granules and are divided into different types based on function.

Page 6: Identification Criteria for Leukocytes

Leukocytes can be identified based on:

• Presence and type of granules.

• Shape and color of the nucleus.

• Color of the cytoplasm which may indicate different types and states of activation.

Page 7: Granulocytes Overview

• Eosinophils: Play a significant role in combating parasitic infections and are involved in allergic responses, making them crucial for immune regulation.

• Basophils: These cells release chemicals such as histamine and heparin, which promote blood flow and inhibit blood clotting, respectively, thus facilitating the inflammatory response.

• Neutrophils: Represent the first line of defense against bacterial infections, engaging in phagocytosis and being characterized by their multi-lobed nuclei.

Page 8: Neutrophils

• Proportion: Constitute 50-70% of all white blood cells in circulation.

• Structure: Characterized by multi-lobed nuclei (3-5 lobes) and small, pale granules.

• Response: Increase in number during acute bacterial infections, indicating an active immune response.

Page 9: Eosinophils

• Proportion: Account for 1-4% of leukocytes.

• Appearance: Identified by a bilobed nucleus and distinctive red granules.

• Function: They engage in phagocytosis of allergens and play vital roles in combating parasitic infections and inflammatory responses.

Page 10: Basophils

• Proportion: Represent 0.5 - 1% of leukocytes.

• Structure: Features include a bilobed nucleus and large purplish-black granules.

• Function: Involved in inflammatory responses, releasing histamine to increase capillary permeability and heparin to inhibit blood clotting.

Agranulocytes

Page 11: General Characteristics

• Appearance: Agranulocytes share a light blue cytoplasm and lack visible granules.

• Nucleus: Can vary in shape, being spherical or kidney-shaped, indicative of their varied roles in the immune response.

Page 12: Lymphocytes

• Proportion: Comprise 20-40% of leukocytes in the bloodstream.

• Structure: Possess a large, dense purple nucleus surrounded by a thin rim of pale blue cytoplasm.

• Role: Key players in the immune response, involved in recognizing and responding to pathogens through various subclasses.

Page 13: Types of Lymphocytes

• T lymphocytes: Essential for managing immune responses, comprising subtypes such as helper T cells which assist other immune cells, and cytotoxic T cells which directly kill infected cells.

• B Lymphocytes: Differentiate into plasma cells that produce antibodies, crucial for targeting specific pathogens.

• Natural Killer Cells: Specialize in targeting and destroying abnormal or infected cells, providing a rapid response to infections and tumor growth.

Page 14: Monocytes

• Proportion: Account for 2 - 8% of leukocytes.

• Appearance: Characterized by a dark purple, kidney-shaped nucleus.

• Function: Transform into macrophages in tissues, promoting phagocytosis and the removal of debris and pathogens.

Page 15: Leukocytes in Order of Abundance

1. Neutrophil

2. Lymphocyte

3. Monocyte

4. Eosinophil

5. Basophil

Leukocyte Disorders

Page 16: Overview of Disorders

• Leukocytosis: Characterized by a high white blood cell count, often a physiological response to infections, inflammation, or stress.

• Leukopenia: Low white blood cell count that decreases the body's ability to fight infections, often a result of drug-induced effects, bone marrow failure, or autoimmune disorders.

Page 17: Leukemia

Leukemia is a malignancy affecting the cells that produce leukocytes, leading to an abnormal proliferation of immature white blood cells. This condition typically results in a decrease in erythrocytes and platelets, leading to anemia (fatigue, weakness) and bleeding issues (petechiae, easy bruising).

Hematopoiesis

Page 18: Hematopoietic Process

Leukocytes (granulocytes and monocytes) originate from stem cells in the bone marrow:

• Lymphoid stem cells: Responsible for producing lymphocytes.

• Myeloid stem cells: Responsible for producing granulocytes and monocytes.

• An illustration of hemostatic pathways and the differentiation process is included.

Hemostasis

Page 20: Learning Objectives

Understand the mechanisms underlying clot formation after vascular injury and the regulatory processes preventing clot formation in normal circumstances.

Page 21: Platelets (Thrombocytes)

• Nature: Cell fragments that play crucial roles in hemostasis; they lack a nucleus and are derived from megakaryocytes in the bone marrow.

Page 22: Hemostasis Overview

This process entails the cessation of bleeding, integrating the actions of clotting factors and substances released from platelets and injured tissues.

Page 23: Phases of Hemostasis

1. Vascular spasm: The initial response causes vasoconstriction to reduce blood loss.

2. Platelet plug formation: Platelets adhere to exposed collagen in the vessel wall and aggregate to form a temporary plug.

3. Coagulation: The formation of a fibrin mesh stabilizes the platelet plug by trapping RBCs, creating a more durable clot.

Page 24: Coagulation Process

Coagulation involves both intrinsic (triggered by damage to blood vessels) and extrinsic pathways (triggered by external damage), which converge into common pathways leading to fibrin formation. ### Steps of the Coagulation Positive Feedback Loop 1. **Tissue Damage**: Injury to blood vessels occurs, releasing signals that initiate the coagulation cascade. 2. **Activation of Intrinsic Pathway**: Damage exposes collagen, activating the intrinsic pathway which is a series of protein reactions leading to amplifying clotting factors. 3. **Activation of Extrinsic Pathway**: The presence of tissue factor (TF) from damaged cells activates the extrinsic pathway quickly. 4. **Convergence of Pathways**: Both intrinsic and extrinsic pathways converge at factor X, leading to thrombin generation. 5. **Thrombin Production**: Thrombin further converts fibrinogen into fibrin, which forms the structural framework of the clot. 6. **Amplification of Clotting**: Thrombin activates additional factors (such as factors V and VIII) that enhance the cascade, thereby amplifying the production of more thrombin and fibrin, solidifying the clot.

Page 25: Coagulation Pathways

• Intrinsic pathway: Involves a complex cascade initiated by damage to the blood vessel, taking longer (3-6 minutes).

• Extrinsic pathway: Provides a quicker response to external damage, activating within approximately 15 seconds.

Page 26: Final Steps in Coagulation

Active factor X combines with calcium to form prothrombin activator, which then activates thrombin that stabilizes the clot by converting fibrinogen into fibrin strands.

Page 31: Clot Elimination

• Clot Retraction: Platelet fibers contract to facilitate the expulsion of serum from the clot, aiding in tissue repair.

• Fibrinolysis: Breakdown of fibrin strands occurs via plasmin after the vessel has healed, ensuring that no residual clot obstructs normal circulation.

Page 32: Limiting Clot Formation

The smooth lining of blood vessels and the secretion of anti-thrombotic substances from endothelial cells prevent the occurrence of undesired clotting within the circulatory system.

Page 34: Thromboembolytic Conditions

Conditions characterized by undesirable clotting (thrombus formation) can obstruct circulation, leading to tissue ischemia and death. These complications are clinically significant and require careful monitoring.

Thromboembolytic Prevention

Anticoagulants are crucial to prevent thrombus formation.

Key anticoagulants include:

- Aspirin: Works by inhibiting platelet aggregation, thereby reducing the ability of platelets to form clots.

- Heparin: An injectable anticoagulant that enhances the activity of antithrombin, which inhibits multiple clotting factors, making it effective for immediate anticoagulation.

- Warfarin: An oral anticoagulant that functions by inhibiting vitamin K-dependent clotting factors, slowing down the clotting process over a longer term.

- Dabigatran: A direct thrombin inhibitor that prevents the formation of fibrin, thus disrupting the clotting cascade.

Page 36: Thromboembolytic Prevention

To prevent thrombus formation, anticoagulants such as aspirin, heparin, warfarin, and dabigatran are used. These medications are crucial in managing patients at risk for thromboembolic disorders such as deep vein thrombosis (DVT) and pulmonary embolism (PE).