Hematologic System: Composition and Function

Hematologic System Composition

• Blood consist of 92% water and 8% solutes
• The body contains about 6 quarts (5.5 L) of blood
• Plasma makes up 50% to 55% of blood volume
• Plasma is an aqueous liquid with organic and inorganic elements (electrolytes)
• Serum is plasma that has been allowed to clot to remove fibrinogen

Blood Function

• Blood maintains homeostasis of the intercellular fluid

Transport

• Transports nutrients to cells, carries wastes away, and transports oxygen to cells or intracellular fluid

Regulation

• Provides intracellular communication, enzymatic inhibitors, and cytokines

Defense

• Provides protection and defense through antibodies and complement

Clotting

• Blood clotting uses self-repair mechanisms, fibrinogen, and fibrin

Hematopoiesis

• It's the process of blood cell production in adult bone marrow or in the liver and/or spleen of the fetus
• Humans require 100 billion new blood cells daily
• Hematopoiesis has two stages: mitosis (proliferation) and maturation (differentiation)
• The ongoing process replaces blood cells that die, age, are killed by disease, or are lost through bleeding

Bone Marrow

• The bone marrow resides in the cavity of bones
• The bone marrow constitutes the primary site of residence of hematopoietic stem cells, and is referred to as myeloid tissue
• Red and yellow denote the presence of marrow
• Located in pelvic bones, vertebrae, cranium and mandible, sternum and ribs, humerus, and femur
• Niches control differentiation of hematopoietic progenitor cells with an osteoblastic niche and vascular niche present

Stem Cells

• Stem cells are found in niches
• Mesenchymal stem cells, or MSCs, are stromal cells able to differentiate into various cell types like osteoblasts, adipocytes, and chondrocytes which produce cartilage
• Hematopoietic stem cells, or HSCs, are progenitors of all hematologic cells
• Hematopoietic stem cells proliferate and differentiate under the control of a variety of cytokines and growth factors in blood cells
• Pluripotent cells can continue to grow into different kinds of tissue and have unlimited differentiation potential
• Multipotent stem cells have limited, but significant, differentiation abilities
• Colony-stimulating factors, or CSFs, are hematopoietic growth factors which stimulate progenitor cells to mature and can be used to increase the amount of neutrophils

Pools of Hematopoiesis

• Occurs in two separate pools
• Stem cell pool is maintained by self-renewal of pluripotent stem cells and partially committed progenitor cells
• Bone marrow pool contains cells proliferating and maturing for release into circulation and stores mature cells for release into peripheral blood, containing those in circulation and those stored around the walls of the blood vessels, referred to as the marginating storage pool, primarily consisting of neutrophils

Factors That Increase Hematopoiesis

• Factors include conversion of yellow bone marrow to hematopoietic red marrow spurred by erythropoietin, which stimulates erythrocyte production
• Also contributes to faster differentiation of progenitor cells
• There is faster proliferation of stem cells into progenitor cells

Erythrocytes

• Are the most abundant blood cells
• Account for 48% in men and 42% in women
• They are responsible for tissue oxygenation and contain hemoglobin
• Have biconcavity and reversible deformity

Biconcavity

• The erythrocytes' shape provides a surface area and volume ratio that are optimal for gas diffusion and deformity

Reversible Deformity

• Enables an erythrocyte to assume a more compact torpedo-like shape, allowing it to squeeze through the microcirculation and return to its normal shape
• The life cycle lasts 120 days

Senescent Erythrocytes

• Macrophages remove older red blood cells (RBCs) from circulation, generally in the spleen
• Cupffer cells in the liver take over removal if this organ is absent or unable to do so
• Heme breaks down to bilirubin and is excreted, while broken down amino acids form globin, and iron is recycled

Erythrocyte Hemoglobin Functions

• Carries oxygen and carbon dioxide (23%), also functions as a buffer, acting as a weak acid

Iron Cycle

• The spleen has red pulp where capillary ends meet and flows through splenic tissue, and tissue is filled with macrophages

Leukocytes

• Leukocytes which include lymphocytes, granulocytes, and monocytes, arise from stem cells in the bone marrow

Progenitor Cells

• Lymphoid progenitors, some of which stay in marrow, and some of which undergo differentiation into the B-cell lineage, migrating into circulation and undertaking further maturation in the peripheral lymphoid organs
• Common myeloid progenitors further differentiate into basophils, mast cells, eosinophils, and megakaryocytes, and granulocyte/monocyte progenitors

Granulocytes

• Granulocytes mature in the bone marrow
• Agranulocytes and monocytes are released into the bloodstream before full maturation
• Growth factors and colony-stimulating factors encourage leukocyte production and maturation

Characteristics of Granulocytes

• They have membrane-bound granules in their cytoplasm, capable of destroying microorganisms
• They are involved in inflammatory and immune functions and catabolize debris ingested during phagocytosis
• They exhibit amoeboid movement or diapedesis to migrate through vessel walls to sites of action

Neutrophils

• Neutrophils are the most numerous at 55%
• They defend against infection and are also referred to as polymorphonuclear neutrophils, or PMNs
• They serve as phagocytes in early inflammation
• Immature forms are bands or stabs, and mature forms are segmented
• They destroy microorganisms and other debris and die in 1-2 days

Eosinophils

• Eosinophils count for 1% to 4%
• They are capable of amoeboid movement and phagocytosis and ingest antigen-antibody complexes and viruses
• Release cytokines and leukotrienes that augment the inflammatory response
• Increase in type I hypersensitivity allergic reactions and asthma
• Helps increase and attack parasitic infections

Basophils

• Basophils make up less than 1% of granulocytes
• They contain histamine and increase at sites of allergic inflammatory reactions and parasitic infection, particularly with exoparasites like ticks
• Secrete inflammatory mediators like histamine and chemotactic factors for eosinophils and neutrophils
• Contribute to the local inflammatory response

Mast Cells

• Mast cells are highly similar to basophils and are the central cells in inflammation that are found in vascularized connective tissue
• Activation and degranulation affect body cells
• Cause increased permeability of blood vessels and smooth muscle contraction

Lymphocytes

• Lymphocytes constitue 36% of leukocytes
• They are the major cells of the immune system
• Includes mature T, B, and plasma cells
• The lifespan extends between days, months, or years depending on the type of cell

Natural Killer (NK) Cells

• Make up from 5% to 10% of leukocytes
• Found mainly in the peripheral blood and spleen
• Kills virally infected and tumor cells and does not have to be induced by antigens
• Produces cytokines involved in the immune responses

Monocytes and Macrophages

• These make up the mononuclear phagocyte system (MPS) and can be found in tissue and lymphoid organs
• Monocytes are precursors to macrophages and dendritic cells
• They provide the main line of defense against bacteria in the bloodstream and cleanses the blood by removing old, injured, or dead blood cells

Macrophages

• Remove damaged, old, and large molecules from circulation and initiate wound healing and tissue remodeling
• Major "antigen-processing" and "antigen-presenting" cells that initiate immune responses

Dendritic Cells

• They extend projections, or dendrites into the tissue, taking on a neuronlike appearance
• It contains processes to initiate immune responses by processing and presenting antigens

Platelets

• These are irregularly-shaped cytoplasmic fragments formed by the fragmentation of megakaryocytes
• Essential for blood coagulation and the control of bleeding
• Incapable of mitotic division
• Granules are generally proinflammatory
• Live for 8-10 days, then are removed by the spleen
• Normal count is 140,000 to 340,000 platelets/mm³

Endomitosis

• Megakaryocyte undergoes DNA replication, yet blocks anaphase and cytokinesis
• Megakaryocyte expands as a result of the doubling of the DNA, causing it to break up into smaller fragments
• Circulates for 8-10 days before it loses functional capacity
• Thrombopoietin and interleukin 11 (IL-11) maintain levels

Lymphoid organs

• Sites of residence, proliferation, differentiation, and function of lymphocytes and mononuclear phagocytes
• Links the hematologic and immune systems

Primary Lymphoid Organs

• Thymus and Bone Marrow

Secondary Lymphoid Organs

• Spleen, lymph nodes, tonsils, and Peyer patches of the small intestine

The Spleen

• It is the largest secondary lymphoid organ and functions

Spleen Functions

• Site of fetal hematopoiesis
• Used for filtering and cleansing of the blood
• Mounts an immune response to blood borne microorganisms
• Functions as a blood reservoir

Splenic Pulp

• Tissue containing macrophages and lymphoid tissue responsible for fetal hematopoiesis

Splenic Removal

• Removal of the spleen will increase risk of encapsulated bacteria infections from lack of immunoglobulin M, often referred to as IgM

Lymph Nodes

• Sites of the development or activity of lymphocytes, monocytes, and macrophages within the lymphatic system
• They provide filtration of the lymph
• Lymph nodes are fibrous capsules partitioned in different compartments, via inward partitions which are extensions which form trabeculae

Lymph nodes Functions

• They are functionally part of the immune and hematologic systems and facilitate the first encounter between antigen and lymphocytes
• Macrophages reside within the lymph nodes and filter the lymph of debris, foreign substances, and microorganisms which perform the function of antigen-processing

Hemostasis

• Definition: Arrest of bleeding- Functions Include
  • Vasculature- Endothelial cells and Sub-endothelial Matrix
  • Platelets Function
  • Blood proteins- Clotting factors

Sequence Following Events

• Vascular injury leads to vasoconstriction
• Formation of a platelet plug occurs
• Tissue factor activates the coagulation cascade
• Formation is dependent on blood clot or secondary hemostasis
• Clot retraction and clot dissolution that is referred to as fibrinolysis

Functions of Platelets

• Helps to regulate blood flow into a damaged site that results in vasoconstriction
• Initiates platelet-to-platelet interactions resulting in formation of a platelet plug
• Activation on depending or either the coagulation by clotting
• It involves the cascade to stimulate the platelet plug
• Initiates repair processes include clot retraction and clot dissolution that is known as fibrinolysis

Platelet Counts

• Normal platelet count is 140,000 to 340,000/mm3.
• Platelet count is below 100,000/mm what results in the result of prolongated clotting time
• Platelet count falls below 20,000/mm bleeding is more likely to occur
• If Platelet numbers are elevated which means there is thrombocytosis and as a result there is increased risk for spontaneous blood clots that may result in:
  • Thrombosis
  • Storkes
  • Heart Attacks

Platelet Plug Formation

• Platelet plug formation dependent on three variables that are:
  • Mediated through binding of platelet receptor of the Von Willbrand factor which is known as(VwF) during the phase of Adhesion
  • Spheres change to spiny shapes that triggers degranulation called -platelet release to release biochemicals
  • Mediated by fibrogen bridges across receptors
  • Clot retracts and strengthens the strands through approximation to the edges

Functions of Clotting Factors

• Dependent on the Fibrin that include Intrinsic and Extrinsic Pathaway:
  • Activated by Hagamen Factor contacts while injuries occur
  • Extrinsic is more dominant

Common Pathway Both Pathways

• Prothrombin turns to thrombin
• Fibrinogen turns to fibrin

Regulatory Factors

• Regulatory factors are dependent on cell surfaces and are located on the endothelial cell

Endothelium

• Endothelium that prevents the formation of spontaneous clots in normal vessels by several anticoagulant mechanisms:
  • Production of nitric oxide (NO)
  • Production Prostacyclin
  • Thrombin
  • Tissue factor inhibitors
  • Degradation clotting factors

Anticoagulant Factors

• Antithrombin 3 which inhibits Clotting factors
• Tissue Pathway inhibits factor 10
• Protiens C and S degrade factor Va and VIIa

CLot lysing

• Limits the size and aids in the remove of blood loss after initial phases

pediatric Differences

• Pediatric Patients blood count is significantly more greater than adults
• As traumas occur to birth which results in cord stimulation there is an increase level of erythopoesis
• Large Number of immature erthyocites are common to full term neonates
• erthyocites in child and premature infants are different
• decreased risk in clotting factors which decreases the Thrombotic complications
• Children have more different Lymphos when referring to Atypical ones
• Neutrophil counts is higher on babies till later in life
• As age goes the differences tend to disappear

Aging System

• Limited chnage in aged compostion
• Erthoctye ifepan is shorter as the life span is shortened.
• iron decreese that occurs whith total iron decreasing.
  • decrease on cells
• T-Cell function is limited at an age
• Humoral is not respnses