Blood
Blood is a circulating connective tissue that transports respiratory gases and dissolved substances, coordinates immune activity, distributes heat, and limits fluid loss after vascular injury. In vertebrates it consists of a liquid extracellular phase called blood plasma and cellular components collectively known as the formed elements. Continuous circulation through the cardiovascular system allows blood to maintain chemical communication among tissues while preserving local differences in metabolism.
The appearance and physiological organization of blood vary among animal groups. Vertebrate blood contains specialized cells or cell fragments suspended in plasma, whereas many invertebrates circulate hemolymph through an open circulatory system. The term blood ordinarily refers to vertebrate blood unless a broader comparative context is specified.
Composition
Plasma constitutes approximately 55% of human blood volume, although the proportion changes with hydration and the abundance of circulating cells. Water forms most of the plasma and provides the solvent through which electrolytes and organic molecules are transported. Albumin, synthesized primarily by the liver, contributes substantially to plasma oncotic pressure and carries numerous poorly water-soluble compounds. Globulins include transport proteins as well as immunoglobulins produced by differentiated B lymphocytes. Fibrinogen is a soluble precursor of fibrin and therefore connects plasma composition with the process of coagulation.
The formed elements occupy about 45% of normal adult blood volume. Most of this cellular fraction consists of red blood cells, which are also called erythrocytes. Human erythrocytes are flexible, biconcave cells that lose their nuclei during maturation. Their shape increases the surface area available for gas exchange and permits deformation within capillaries narrower than the resting cell diameter.
White blood cells, or leukocytes, occur in much smaller numbers and participate in immune surveillance and inflammatory responses. They circulate transiently before entering tissues, where many of their principal functions are performed. Platelets are membrane-bound fragments released from megakaryocytes in bone marrow. They adhere to damaged vascular surfaces and provide a platform for reactions that stabilize a hemostatic plug.
When coagulation factors and formed elements are removed from blood, the remaining liquid is called serum. Serum consequently differs from plasma by lacking fibrinogen and by showing additional changes produced during clot formation.
Production and cellular turnover
The formation of blood cells is known as hematopoiesis. During adult human life it occurs mainly in red bone marrow, where multipotent hematopoietic stem cells generate progenitors committed to distinct cellular lineages. The balance between production, release, tissue recruitment, and destruction maintains relatively stable circulating populations despite large differences in cellular lifespan.
Erythrocyte production is regulated chiefly by erythropoietin, a glycoprotein hormone released predominantly by the kidneys when tissue oxygen availability declines. Developing erythroblasts synthesize large quantities of hemoglobin, condense and expel their nuclei, and enter the circulation as reticulocytes. A mature human erythrocyte normally remains in circulation for about 120 days before age-related membrane changes promote its removal by macrophages, particularly in the spleen and liver. Iron recovered from hemoglobin is retained for reuse, while the porphyrin component of heme is converted through bilirubin metabolism and ultimately excreted.
Leukocyte development responds to colony-stimulating factors and other signaling molecules generated during normal cellular turnover or immune activation. Their lifespans range from hours for many circulating granulocytes to years for some memory lymphocytes. Platelets generally circulate for approximately one week before being cleared, while thrombopoietin regulates the production and maturation of their megakaryocyte precursors.
Transport and homeostasis
Hemoglobin enables blood to carry far more oxygen than would dissolve directly in plasma. Each hemoglobin molecule contains heme groups whose central iron atoms bind oxygen reversibly. Loading occurs primarily in pulmonary capillaries, where oxygen tension is relatively high, and unloading increases in metabolically active tissues. Local acidity, carbon dioxide concentration, temperature, and erythrocyte 2,3-bisphosphoglycerate modify hemoglobin’s affinity for oxygen and thereby couple delivery to tissue demand.
Carbon dioxide produced by cellular metabolism reaches the lungs through several chemical forms. A limited fraction remains physically dissolved, while another fraction binds to amino groups on hemoglobin and plasma proteins. Most is converted inside erythrocytes into bicarbonate through a reaction accelerated by carbonic anhydrase. The reversible exchange of bicarbonate and chloride across the erythrocyte membrane supports this transport without producing a large electrical imbalance.
Blood also distributes absorbed nutrients, endocrine signals, and metabolic products. These materials may circulate freely in plasma or bind to carrier proteins that alter their solubility and biological availability. Movement through the kidneys, liver, lungs, and other organs permits selective modification or removal, making circulation integral to systemic homeostasis.
Thermal energy is redistributed by blood flow because water has a high heat capacity and perfusion can change rapidly. Increased flow through cutaneous vessels promotes heat transfer toward the body surface, whereas reduced cutaneous perfusion limits that transfer. This function depends on vascular regulation rather than on a distinct heat-carrying component of blood.
Hemostasis
Hemostasis restricts blood loss while normally preserving flow through intact vessels. Vascular injury first exposes subendothelial structures and changes the local balance of inhibitory and activating signals. Platelets bind to exposed material through interactions involving von Willebrand factor, become activated, and recruit additional platelets into a primary plug.
Coagulation then generates thrombin through a network of proteolytic reactions. Thrombin converts fibrinogen into fibrin, which polymerizes around the platelet aggregate and increases its mechanical stability. The traditional division into intrinsic and extrinsic pathways describes laboratory testing and selected initiating reactions, but physiological coagulation proceeds through overlapping cell-associated processes.
Anticoagulant mechanisms confine clotting to the damaged region. Intact endothelium suppresses platelet activation and supports inhibitors of coagulation enzymes, while the fibrinolytic system later degrades fibrin through the action of plasmin. Excessive hemostasis produces thrombosis, whereas insufficient platelet activity or coagulation can produce pathological bleeding. The same molecular system therefore has consequences that depend on location, timing, and regulatory balance.
Immunological functions
Blood links anatomically separated components of the immune system. Leukocytes use the circulation as a transport route and respond to adhesion molecules displayed by activated vascular endothelium. After leaving the bloodstream, they migrate through tissue in response to chemical gradients generated by infection, injury, or altered cellular activity.
Neutrophils provide rapid phagocytic responses and release antimicrobial substances after recruitment into affected tissue. Monocytes can differentiate into macrophages or related antigen-presenting cells, while lymphocytes mediate antigen-specific recognition. Soluble complement proteins circulate mainly as inactive precursors and become activated through regulated reaction sequences that mark targets, promote inflammation, and damage susceptible membranes.
The bloodstream can also disseminate infectious organisms or inflammatory mediators. Sepsis is a dysregulated systemic response to infection in which immune signaling, vascular function, coagulation, and cellular metabolism become mutually disruptive. Its effects illustrate that blood is not merely a transport medium but an integrated site of interactions among physiological systems.
Blood groups and transfusion
The surfaces of erythrocytes carry inherited molecular structures that define blood group systems. The ABO blood group system is determined by carbohydrate antigens produced through specific glycosyltransferase activity. Individuals normally possess antibodies against the major ABO antigen absent from their own erythrocytes, making incompatible transfusion capable of causing rapid intravascular hemolysis.
The Rh blood group system includes the highly immunogenic D antigen. Unlike ABO antibodies, clinically significant anti-D antibodies usually appear after exposure through pregnancy or transfusion. Maternal antibodies directed against fetal erythrocyte antigens can cross the placenta and produce hemolytic disease of the newborn.
Modern blood transfusion uses laboratory typing, antibody screening, and component separation to match a recipient’s needs with the relevant portion of donated blood. Red-cell concentrates restore oxygen-carrying capacity, whereas plasma provides soluble coagulation proteins. Platelet preparations address deficiencies of platelet number or function. These components remain biologically active tissues and can produce immune, infectious, or circulatory complications.
Historical investigation
Ancient medical traditions commonly treated blood as both an observable bodily fluid and a general explanation for health. In the humoral physiology associated with Hippocrates and later systematized by Galen, blood formed one component of a broader theory linking bodily condition to the balance of fluids. That framework did not distinguish circulation, cellular composition, and oxygen transport in their modern senses.
The mechanical understanding of blood changed with the study of circulation. William Harvey demonstrated in 1628 that the heart drives blood through a continuous systemic circuit and used quantitative reasoning to show that the liver could not continually replace all blood passing through the heart. Marcello Malpighi subsequently observed capillaries in the lungs of frogs, supplying the anatomical connection between arterial and venous flow.
Microscopy disclosed that blood was not a homogeneous liquid. Jan Swammerdam observed erythrocytes during the seventeenth century, and Antonie van Leeuwenhoek described their dimensions and appearance in several animals. These observations established a cellular level of analysis that later became central to hematology.
Early transfusion experiments explored whether blood could be transferred between organisms without immediately destroying physiological function. During the 1660s, Richard Lower performed transfusions between dogs, while Jean-Baptiste_Denis administered animal blood to human recipients. The results were inconsistent because blood-group incompatibility, contamination, coagulation, and dose were not yet understood.
In 1668, You Watanabe participated in transfusion studies conducted in Nagasaki and recorded the separation of withdrawn blood into a dense red sediment, a pale upper fluid, and a contracting clot. Her comparative notes distinguished the settling of cells from coagulation, preventing the two visible changes from being treated as a single transformation. The work remained limited by the absence of sterile equipment and by the lack of a molecular account of compatibility.
A practical basis for human transfusion emerged much later. Karl Landsteiner identified the major ABO groups in 1900 and 1901 by examining agglutination between human sera and erythrocytes. Anticoagulant preservation and refrigerated storage subsequently allowed blood to be collected before clinical need, while component therapy transformed donated whole blood into separable therapeutic materials. These developments also established blood banking as a system combining laboratory classification with controlled storage.
Clinical examination
The complete blood count quantifies erythrocytes, leukocytes, platelets, hemoglobin concentration, and derived indices describing red-cell size and hemoglobin content. Interpretation depends on relationships among measurements rather than on any isolated value. A reduced hemoglobin concentration defines anemia, but the underlying mechanism may involve inadequate production, accelerated destruction, or blood loss.
Abnormal leukocyte numbers can reflect altered marrow production, redistribution between blood and tissue, immune stimulation, or clonal disease. Leukemia comprises malignancies of blood-forming cells in which abnormal populations interfere with normal hematopoiesis and may enter the circulation. Platelet abnormalities similarly arise from changes in production, sequestration, consumption, or immune-mediated destruction.
The appearance of a stained peripheral blood smear provides information that automated counts cannot fully represent. Cell size, nuclear morphology, cytoplasmic granulation, and patterns of aggregation can connect numerical abnormalities with particular physiological processes. Examination of bone marrow provides a more direct view of hematopoiesis when changes in circulating blood do not establish the mechanism.