Blood Composition: What Blood Is Made Of and How It Works

Plasma: The Liquid Foundation

Blood plasma is approximately 92% water by volume, with the remaining 8% consisting of dissolved proteins (7%), electrolytes (0.9%), and other solutes including glucose, lipids, amino acids, hormones, waste products, and dissolved gases. This straw-colored fluid serves as the transport medium for everything the circulatory system delivers: nutrients absorbed from the gut, hormones released by endocrine glands, antibodies produced by immune cells, waste products destined for the kidneys and liver, and heat generated by metabolically active tissues that must be distributed or dissipated.

The three major plasma protein groups are albumin (60% of total plasma protein, produced by the liver at 10 to 15 grams per day), globulins (35%, including immunoglobulins, transport proteins, and complement factors), and fibrinogen (4%, the inactive precursor to fibrin used in clot formation). Albumin's primary function is maintaining oncotic pressure, the osmotic force that draws water from the interstitial space back into capillaries. At a concentration of approximately 35 to 50 grams per liter, albumin accounts for about 80% of plasma oncotic pressure. When albumin levels drop (as in liver disease or malnutrition), fluid leaks from capillaries into tissues, causing edema.

Plasma electrolytes maintain precise concentrations critical for cell function: sodium at 135 to 145 millimoles per liter (the primary extracellular cation), potassium at 3.5 to 5.0 mmol/L (critical for cardiac and neural function), chloride at 96 to 106 mmol/L, bicarbonate at 22 to 26 mmol/L (the primary blood buffer), and calcium at 2.2 to 2.6 mmol/L. These concentrations are regulated within narrow ranges by the kidneys, with deviations of even 10 to 20% capable of causing dangerous cardiac arrhythmias, seizures, or muscle paralysis.

Red Blood Cells: Oxygen Transport Specialists

Red blood cells (erythrocytes) are the most abundant cells in blood, numbering approximately 4.5 to 5.5 million per microliter in healthy adults (roughly 25 trillion total in the body). Each RBC is a biconcave disc approximately 7.5 micrometers in diameter and 2.5 micrometers thick at the edges, tapering to about 1 micrometer at the center. This distinctive shape maximizes surface area relative to volume (providing about 30% more membrane surface than a sphere of the same volume), facilitating gas exchange, while also allowing the cell to deform and pass through capillaries as narrow as 3 micrometers in diameter.

Mature red blood cells in mammals are unique among body cells because they lack a nucleus, mitochondria, and other organelles, which were expelled during the final stages of development in the bone marrow. This extreme specialization serves two purposes: it frees up internal space for approximately 270 million hemoglobin molecules per cell (each capable of binding four oxygen molecules), and it eliminates mitochondrial oxygen consumption so the cell does not use the oxygen it transports. Each hemoglobin molecule consists of four globin protein chains (two alpha and two beta in adult hemoglobin A), each containing an iron-centered heme group that reversibly binds one O2 molecule.

Oxygen binding by hemoglobin follows a sigmoidal (S-shaped) dissociation curve due to cooperative binding: the binding of the first O2 molecule causes conformational changes that make subsequent binding easier. This creates efficient oxygen loading in the lungs (where partial pressure of O2 is high, approximately 100 mmHg, achieving 97 to 99% saturation) and efficient unloading in the tissues (where pO2 is 20 to 40 mmHg, dropping saturation to 60 to 75%). The Bohr effect further enhances delivery: lower pH and higher CO2 in metabolically active tissues shift the curve rightward, promoting oxygen release precisely where it is most needed.

Red blood cells have a lifespan of approximately 120 days, after which their aging membranes become rigid and are recognized and removed by macrophages in the spleen and liver (a process called extravascular hemolysis). The hemoglobin is broken down: globin chains are recycled as amino acids, iron is salvaged and returned to the bone marrow via transferrin, and the porphyrin ring is converted to bilirubin (processed by the liver and excreted in bile). The body replaces roughly 200 billion red blood cells daily, maintaining a constant circulating mass through erythropoiesis in the bone marrow driven by erythropoietin (EPO) hormone released by the kidneys in response to tissue oxygen levels.

White Blood Cells: The Immune Army

White blood cells (leukocytes) number only 4,000 to 11,000 per microliter of blood (roughly 1 WBC for every 700 RBCs), but their role in defense against infection is indispensable. Five types circulate in blood, each with distinct functions and morphologies visible under microscopy after staining.

Neutrophils (50 to 70% of WBCs, 2,500 to 7,000 per microliter) are the first responders to bacterial infection. These short-lived cells (6 to 12 hours in blood, 1 to 4 days in tissues) engulf and kill bacteria through phagocytosis, deploying reactive oxygen species, degradative enzymes from their granules, and neutrophil extracellular traps (NETs) made of expelled DNA strands that snare pathogens. Pus is largely composed of dead neutrophils, killed bacteria, and tissue debris.

Lymphocytes (20 to 40% of WBCs) include T cells, B cells, and natural killer (NK) cells that drive the adaptive immune response. T cells recognize specific antigens presented on cell surfaces, coordinating immune attacks (helper T cells) or directly killing infected cells (cytotoxic T cells). B cells differentiate into plasma cells that produce antibodies at rates of up to 2,000 molecules per second per cell. NK cells patrol for cells that have downregulated MHC class I molecules, a common viral immune evasion strategy, and destroy them without prior sensitization.

Monocytes (2 to 8% of WBCs) circulate for 1 to 3 days before migrating into tissues and differentiating into macrophages or dendritic cells. Tissue macrophages are long-lived phagocytes that clear cellular debris, present antigens to T cells, and secrete cytokines that coordinate inflammatory responses. Different tissues host specialized macrophage populations: Kupffer cells in the liver, alveolar macrophages in the lungs, microglia in the brain, and osteoclasts in bone.

Eosinophils (1 to 4% of WBCs) specialize in combating parasitic infections, releasing toxic granule proteins (major basic protein, eosinophil cationic protein) onto multicellular parasites too large to phagocytose. They also modulate allergic responses, and elevated eosinophil counts are a hallmark of allergic conditions and parasitic infections. Basophils (less than 1% of WBCs) are the rarest circulating leukocytes, containing granules loaded with histamine and heparin that they release during allergic and inflammatory reactions, amplifying the immune response and promoting vasodilation.

Platelets and the Clotting Cascade

Platelets (thrombocytes) are small, disc-shaped cell fragments approximately 2 to 3 micrometers in diameter, produced in the bone marrow by megakaryocytes that extend cytoplasmic processes into sinusoidal blood vessels where shear forces fragment them into 2,000 to 3,000 platelets per megakaryocyte. Normal platelet counts range from 150,000 to 400,000 per microliter, and each platelet circulates for 8 to 10 days before being removed by the spleen. Despite lacking a nucleus, platelets contain mitochondria, granules packed with clotting factors and growth factors, a cytoskeleton capable of shape change, and surface receptors that detect damaged blood vessel walls.

When a blood vessel is injured, the exposed subendothelial collagen triggers the hemostatic response. Primary hemostasis (within seconds) involves platelet adhesion via von Willebrand factor bridges, platelet activation (shape change from disc to spiny sphere with pseudopod extension), degranulation (releasing ADP, thromboxane A2, and serotonin that recruit additional platelets), and platelet aggregation into a temporary plug. Secondary hemostasis (over minutes) involves the coagulation cascade, a series of sequential enzyme activations (factors I through XIII) that converges on the conversion of fibrinogen to fibrin, which polymerizes into insoluble strands that reinforce the platelet plug into a stable clot.

The coagulation cascade has two initiation pathways: the extrinsic pathway (triggered by tissue factor exposed by injured cells, measured clinically by prothrombin time/INR) and the intrinsic pathway (triggered by contact with foreign surfaces like exposed collagen, measured by partial thromboplastin time). Both converge at factor X activation, leading to thrombin generation and fibrin formation. The system is balanced by natural anticoagulants (antithrombin, protein C, protein S) that prevent clotting from spreading beyond the injury site, and by fibrinolysis (plasmin-mediated clot dissolution) that gradually removes clots once healing is complete.

Blood Types and Transfusion Science

The ABO blood group system, discovered by Karl Landsteiner in 1901, is determined by which carbohydrate antigens are present on the red blood cell surface. Type A individuals have A antigens and produce anti-B antibodies in plasma. Type B individuals have B antigens and produce anti-A antibodies. Type AB individuals have both antigens and produce neither antibody (universal plasma donors). Type O individuals have neither antigen but produce both anti-A and anti-B antibodies (universal red cell donors). These "naturally occurring" antibodies develop in infancy in response to similar carbohydrate structures on gut bacteria, without prior transfusion exposure.

The Rh system, the second most important blood group, involves the RhD antigen: Rh-positive individuals have it (approximately 85% of the population), while Rh-negative individuals do not. Unlike ABO antibodies, anti-Rh antibodies develop only after exposure through transfusion or pregnancy. Rh incompatibility becomes clinically significant when an Rh-negative mother carries an Rh-positive fetus: fetal red blood cells entering maternal circulation during delivery can sensitize her immune system, causing hemolytic disease of the newborn in subsequent Rh-positive pregnancies. Rh immunoglobulin (RhoGAM) injection at 28 weeks gestation and after delivery prevents this sensitization.

Beyond ABO and Rh, over 360 red cell antigens in 43 blood group systems have been identified. Most rarely cause transfusion reactions, but some (Kell, Duffy, Kidd) can trigger severe hemolytic reactions in sensitized recipients. Pre-transfusion compatibility testing (crossmatching) mixes donor red cells with recipient plasma to detect antibodies against any donor antigens, taking 30 to 60 minutes. In emergencies, type O-negative (Rh-negative) red cells and AB plasma can be given without crossmatching, though this practice is reserved for life-threatening hemorrhage when the delay of crossmatching is unacceptable.

Hematopoiesis: How Blood Cells Are Made

All blood cells originate from hematopoietic stem cells (HSCs) in the bone marrow, which possess two defining properties: self-renewal (maintaining the stem cell pool throughout life) and pluripotency (ability to differentiate into any blood cell type). In adults, active hematopoiesis occurs primarily in the flat bones (pelvis, sternum, vertebrae, ribs, skull), with the red marrow of a healthy adult producing approximately 500 billion blood cells per day. HSCs represent only about 1 in 10,000 to 1 in 100,000 bone marrow cells, maintained in specialized niches near the bone surface where signals from osteoblasts and stromal cells regulate their quiescence, self-renewal, and differentiation decisions.

HSCs first differentiate into either common myeloid progenitors (giving rise to red blood cells, platelets, neutrophils, monocytes, eosinophils, and basophils) or common lymphoid progenitors (giving rise to T cells, B cells, and NK cells). Each lineage is driven by specific combinations of growth factors: erythropoietin (EPO) for red blood cells, thrombopoietin (TPO) for megakaryocytes and platelets, G-CSF and GM-CSF for granulocytes, and various interleukins for lymphocyte development. This system responds dynamically to the body's needs: during infection, granulocyte production accelerates 10-fold or more, while blood loss or hypoxia triggers EPO release from the kidneys, stimulating red blood cell production that can triple within 5 to 7 days.

Blood as a Diagnostic Window

A complete blood count (CBC), the most commonly ordered laboratory test worldwide, provides a comprehensive snapshot of blood composition: red cell count, hemoglobin concentration (normal: 12 to 17 g/dL), hematocrit (percentage of blood volume occupied by red cells, normal: 36 to 52%), mean corpuscular volume (average red cell size), white cell count with differential (percentages of each type), and platelet count. Deviations from normal ranges signal specific conditions: low hemoglobin indicates anemia (which may result from iron deficiency, vitamin B12 deficiency, chronic disease, bone marrow failure, or blood loss), elevated white cells suggest infection or leukemia, and low platelets indicate bleeding risk from causes ranging from immune destruction to production failure.

Beyond the CBC, blood chemistry panels measure metabolic markers (glucose, electrolytes, kidney function, liver enzymes), coagulation studies assess clotting capability, and specialized tests detect specific antibodies, hormones, tumor markers, or drug levels. The blood carries chemical signatures of virtually every organ system's function, making it the single most informative diagnostic specimen in medicine. A standard 10 mL blood draw can yield dozens of measurements that together paint a detailed picture of metabolic, immune, endocrine, and organ health.