CH 27

Blood clot

A blood clot is a meshwork of protein strands that stabilizes the platelet plug. The strands are made of fibrin. Fibrin is the end product of the coagulation cascade.

Blood cell counts throughout the lifespan

Blood cell counts rise above adult levels at birth and then gradually decline throughout childhood.

Blood composition and age

Blood composition changes little with age. A delay in erythrocyte replenishment may occur after bleeding, presumably because of iron deficiency. Lymphocyte function appears to decrease with age. Particularly affected is a decrease in cellular immunity. Platelet adhesiveness probably increases with age.

Erythrocytes

Erythrocytes are the most abundant cells of the blood, occupying approximately 48% of the blood volume in men and approximately 42% in women. Erythrocytes are responsible for tissue oxygenation.

Erythropoiesis

Erythropoiesis (production of erythrocytes) is regulated by erythropoietin. Erythropoietin is secreted by the kidneys in response to tissue hypoxia and causes a compensatory increase in erythrocyte production if the oxygen content of the blood decreases because of anemia, high altitude, or pulmonary disease.

Fibrinolysis

Fibrinolysis (breakdown of blood clots) is the function of the plasminogen-plasmin system. Plasmin is a degrading enzyme of fibrin clots. It is produced from plasminogen by the activation of plasminogen activators (t-PA, u-PA), thrombin, fibrin, factor XIIa, factor XIa, and kallikrein. Products of fibrinolysis include fibrin degradation products, such as D-dimer.

Granulocytes and monocytes

Granulocytes and monocytes in the blood develop from common myeloid progenitor cells in the bone marrow under the direction of several growth factors, including stem cell factor, IL-3, and GM-CSF.

Hematopoiesis

Hematopoiesis, or blood cell production, occurs in the liver and spleen of the fetus and in the bone marrow after birth. Hematopoiesis involves two stages, proliferation and maturation. Hematopoiesis continues throughout life to replace blood cells that grow old and die, are killed by disease, or are lost through bleeding.

Hemoglobin

Hemoglobin, the oxygen-carrying protein of the erythrocyte, enables the blood to transport 100 times more oxygen than could be transported dissolved in plasma alone.

Hemostasis

Hemostasis, or arrest of bleeding in damaged vessels, involves the following: (1) vasoconstriction. (2) damage to the endothelium and exposure of connective tissue, resulting in formation of a platelet plug; (3) activation of the clotting cascade; (4) formation of a blood clot; and (5) activation of fibrinolysis for clot retraction and clot dissolution.

Leukocytes

Leukocytes are fewer in number than erythrocytes and constitute approximately 5000 to 10,000 cells/mm3 of blood. Leukocytes defend the body against infection and remove dead or injured host cells. Leukocytes are classified as granulocytes (neutrophils, basophils, eosinophils) or agranulocytes (monocytes, macrophages, lymphocytes).

Lymphocytes

Lymphocytes are the primary cells of the immune response.

Plasma

Plasma, the liquid portion of the blood, contains two major groups of proteins, albumins and globulins.

Platelet activation

Platelet activation involves three linked processes: (1) adhesion; (2) activation; and (3) aggregation.

Platelet count at birth

Platelet counts in full-term infants are comparable with those in adults and remain so throughout childhood.

Platelets

Platelets are not cells; they are disk-shaped cytoplasmic fragments. Platelets are essential for blood coagulation and control of bleeding.

Platelets

Platelets develop from megakaryocytes by a process called endomitosis, which is controlled by thrombopoietin. During endomitosis, the megakaryocytes undergo mitosis but not cell division and the cytoplasm and plasma membrane fragment into platelets.

Regulation of hematopoiesis

Regulation of hematopoiesis occurs in specialized microenvironments (niches) in the bone marrow (an osteoblastic niche and a vascular niche) in which hematopoietic stem cells are signaled to undergo differentiation through the effects of multiple cytokines and chemokines and direct contact with osteoblasts (osteoblastic niche) or vascular endothelial cells (vascular niche), as well as several other specialized cells, including CAR cells and nestin-expressing cells.

Hematopoietic growth factors

Specific hematopoietic growth factors (e.g., colony-stimulating factors) are necessary for the adequate production of myeloid, erythroid, lymphoid, and megakaryocytic lineages.

Tests of bone marrow function

Tests of bone marrow function include bone marrow aspiration and bone marrow biopsy. Cells contained in the marrow specimen are assessed with respect to the following: (1) relative numbers of stem cells and their developing daughter cells; and (2) morphologic structure.

The MPS

The MPS is composed of macrophages in tissue and lymphoid organs. The MPS is the main line of defense against bacteria in the bloodstream and cleanses the blood by removing old, injured, or dead blood cells, antigen-antibody complexes, and macromolecules.

Blood in infants

The average blood volume of an infant is 75 to 77 mL/kg, which is similar to that of older children and adults. In response to the change from a placental to a pulmonary oxygen supply during the first few days of life, levels of erythropoietin and the rate of blood cell formation decrease. The normal erythrocyte life span is 60 to 80 days in full-term infants, 20 to 30 days in premature infants, and 120 days in children, adolescents, and adults.

The cellular elements of blood

The cellular elements of blood are the erythrocytes (red blood cells), leukocytes (white blood cells), and platelets (thrombocytes). Blood consists of cells suspended in a solution of about 90% water and 10% solutes. In adults, the total blood volume is approximately 5.5 L.

The coagulation cascade

The coagulation cascade is composed of intrinsic and extrinsic pathways, with the extrinsic pathway being dominant. The intrinsic pathway is initiated by TF that forms a complex with the TF-VIIa complex.

The endothelium

The endothelium prevents the formation of spontaneous clots in normal vessels by several anticoagulant mechanisms, including by production of NO and PGI2, thrombin inhibitors (antithrombin III), and tissue factor inhibitors (tissue factor pathway inhibitors) and by the degradation of activated clotting factors (thrombomodulin, protein C).

The eosinophil count at birth

The eosinophil count is high in the first year of life and is higher in children than in adolescents and adults. Monocyte counts are high in the first year of life and decrease to adult levels.

Iron

The iron cycle reuses iron released from old or damaged erythrocytes. Iron binds to transferrin in the blood, is transported to macrophages of the MPS, and is stored in the cytoplasm as ferritin. Iron homeostasis is controlled by hepcidin, a small hormone produced by hepatocytes, which regulates ferroportin, the principal transporter of iron from stores in hepatocytes and macrophages and from intestinal cells that take up dietary iron.

The lymph nodes

The lymph nodes are the site of development or activity of large numbers of lymphocytes, monocytes, and macrophages.

Lymphocyte count at birth

The lymphocyte count is high at birth, rises further during the first year of life, and steadily declines until lower adult volumes are reached.

The lymphoid organs

The lymphoid organs are classified as primary (thymus and bone marrow) or secondary (spleen, lymph nodes, tonsils, and Peyer patches of the small intestine). The lymphoid organs are sites of residence, proliferation, differentiation, and function of lymphocytes and mononuclear phagocytes.

The neutrophil count at birth

The neutrophil count is very high at birth, falls to adult ranges after 2 weeks, and is the same as that of adults by 4 years of age.

Neutrophils

The neutrophil is the most abundant leukocyte (approximately 55% of the leukocytes) and is the primary granulocyte that defends against infections.

The spleen

The spleen is the largest of the secondary lymphoid organs and functions as the site of hematopoiesis in the fetus, filters and cleanses the blood, and is a reservoir for lymphocytes and other blood cells.

Bone marrow

Bone marrow consists of red (hematopoietic) marrow (blood vessels, mononuclear phagocytes, stem cells, blood cells in various stages of differentiation, stromal cells), and yellow marrow (fatty tissue). The bone marrow contains multiple populations of stem cells; mesenchymal stem cells develop into fibroblasts, osteoclasts, and adipocytes and hematopoietic stem cells develop into blood cells.