Major Componments of Blood

Blood is a specialized connective tissue in which cells are suspended in fluid extracellular material called plasma (ECM/extracellular matrix). When blood leaves the circulatory system, either in a test tube or in the ECM surrounding blood vessels, plasma proteins (coagulation factors) react with one another to produce a clot, which includes formed elements and a pale yellow liquid called serum. Serum contains growth factors and other proteins released from platelets during clot formation, which confer biological properties very different from those of plasma.

Collected blood in which clotting is prevented by the addition of anticoagulants can be separated by centrifugation into layers that reflect its heterogeneity. Erythrocytes make up the sedimented material and their volume, normally about 45% of the total blood volume in healthy adults, is called hematocrit. The straw-colored, translucent, slightly viscous supernatant comprising 55% at the top half of the centrifugation tube is the plasma. A thin gray-white layer called the buffy coat between the plasma and the hematocrit, about 1% of the volume, consists of leukocytes and platelets, both less dense than erythrocytes.

Function of the Blood Tissue

  • O2 is bound mainly to hemoglobin in erythrocytes and is much more abundant in arterial than venous blood, while CO2 is carried in solution as CO2 or HCO3, in addition to being hemoglobin-bound.
  • Nutrients are distributed from their sites of synthesis or absorption in the gut, while metabolic residues are collected from cells all over the body and removed from the blood by the excretory organs.
  • Hormone distribution in blood permits the exchange of chemical messages between distant organs regulating normal organ function.
  • Blood also participates in heat distribution, and the regulation of body temperature.
  • Blood maintain the acid-base and osmotic balance.
  • Blood can form clotting when bleeding happens, the hemostasis.
  • Leukocytes, complements, and antibodies have diversified functions and are one of the body's chief defenses against infection.

Plasma

Plasma is an aqueous solution, pH 7.35~7.45 (in normal conditions), containing substances of low or high molecular weight that make up 7% of its volume. The dissolved components are mostly plasma proteins, but they also include nutrients, respiratory gases, nitrogenous waste products, hormones, and inorganic ions (electrolytes). Through the capillary walls, the low-molecular-weight components of plasma (e.g., most drugs) are in equilibrium with the interstitial fluid of the tissues. Thus, the composition of plasma is usually an indicator of the mean composition of the extracellular fluids in tissues.

Major plasma proteins

  • Albumin, the most abundant plasma protein, is made in the liver and serves primarily to maintain the osmotic pressure of the blood.
  • alpha-Globulins and beta-globulins, made by liver and other cells, include transferrin and other transport factors; fibronectin; prothrombin and other coagulation factors; lipoproteins and other proteins entering blood from tissues.
  • gamma-Globulins, which are immunoglobulins (antibodies) secreted by plasma cells in many locations.
  • Fibrinogen, the largest plasma protein, also made in the liver, which, during clotting, polymerizes as insoluble, cross-link fibers of fibrin that block blood loss from small vessels.
  • Complement proteins, a system of factors important in inflammation and destruction of microorganisms.

RBCs

  • Human erythrocytes normally survive in the circulation for about 120 days. After 120 days, defects in the membrane's cytoskeletal lattice or ion transport systems begin to produce swelling or other shape abnormalities, as well as changes in the cells' surface oligosaccharide complexes. These RBCs are removed from the circulation mainly by macrophages ot the spleen, liver, and bone marrow.
  • Erythrocyte differentiation includes loss of the nucleus and organelles, shortly before the cells are released bone marrow into the circulation. Lacking mitochondria, erythrocytes rely on anaerobic glycolysis for their minimal energy needs.
  • The combination of hemolgobin with carbon monoxide (CO) is irreversible, howevver, reducing the cells' capacity to ransport O2 and CO2.

Leukocytes

Leukocytes leave the blood and migrate to the tissues where they become functional and perform various activities related to immunity. According to the type of cytoplasmic granules and their nuclear morphology, leukocytes are divided into two groups: granulocytes and agranulocytes. All granulocytes are terminally differentiated cells with a life span of only a few days. Their Golgi complexes and rough ER are poorly developed. They have few mitochondria and depend largely on glycolysis for their low energy needs. Granulocytes normally die by apoptosis in the connective tissue. The resulting cellular debris is removed by macrophages and, like all apoptotic cell death, does not itself elicit an inflammatory response.

  • Granulocytes: neutrophils, esoinophils, and basophils
  • Agranulocytes: lymphocytes and monocytes

Neutrophils

Mature neutrophils consitute 54% to 62% of circulating leukocytes; circulating immature forms raise this value by 3% to 5%. In females, the inactive X chromosome may appear as a drumstick-like appendage on one of the lobes of the nucleus although this characteristic is not obviious in every neutrophil. Neutrophils are inactive and spherical while circulating but become actively amoeboid during diapedesis and upon adhering to solid substrates such as collagen in the ECM.

Neutrophils are active phagocytes of bacteria and other small particles and are usually the first leukocytes to arrive at sites of infection, where they actively pursue bacterial cells using chemotaxis. The cytoplasmic granules of neutrophils provide the cells' functional activities and are of two main types (primary granules and secondary granules). Azurophilic primary granules resemble lysosomes as large, dense vesicles and have a major role in both killing and degrading engulfed microorganisms. They contain proteases and antibacterial proteins, including: 1.myeloperoxidase/MPO, which generates hypochlorite and other agents toxic to bacteria; 2.lysozyme, which degrades components of bacterial cell walls; and 3.defensins, small cysteine-rich proteins that bind and disrupt the cell membranes of many types of bacteria and other microorganisms. Specific secondary granules are smaller, less dense, and have diverse functions, including secretion of various ECM-degrading enzymes such as collagenases, delivery of additional bactericidal proteins to the phagolysosomes, and insertion of new cell components.

Activated neutrophils at infected or injured sites also have important roles in the inflammatory response, including the release of chemokines that attract other leukocytes; cytokines that direct activites of these and local cells of the tissue; and the release of lipid mediators of inflammation.

Neutrophils are short-lived cells with a half-life of 6 to 8 hours in blood and a life span of 1 to 4 days in connective tissues before dying by apooptosis.

Eosinophils

Eosinophils are far less numerous than neutrophils, constituting only 1% to 3% of leukocytes. The main identifying characteristic is the abundance of large, acidophilic specific granules typically staining pink or red. Ultrastructurally the eosinophilic specific granules are seen to be oval in shape, with flattened crystalloid cores containing major basic protein/MBP, an arginine-rich factor that act to kill parasitic worms or helminths. Eosinophils also modulate inflammatory responses and allergies.

Basophils

The specific granules in basophils contain heparin and other sulfated GAGs, much histamine and various other mediators of inflammation. By migrating into connective tissues, basophils appear to supplement the function of mast cells. Like mast cells, basophils secretion these granules in response to certain antigens and allergens.

Lymphocytes

By far the most numerous type of agranulocyte in normal blood smears of CBCs, lymphocytes constitute a family of leukocytes with spherical nuclei. Although they are morphologically similar, lymphocytes can be subdivided into functional groups by distinctive surface molecules (called "cluster of differentiation" or CD markers) that can be distinguished using antibodies wtih immunocytochemistry or flow cytometry. Major classes include B lymphocytes, helper and cytotoxic T lymphocytes (CD4+ and CD8+, respectively), and natural killer (NK) cells.

Lymphocytes vary in life span according to their specific functions; some live only a few days and others survive in the circulating blood or other tissues for many years.

Monocytes

Monocytes are agranulocytes that are precursor cells of macrophages, osteoclasts, microglia, and other cells of the mononuclear phagocyte system in connective tissue. All monocyte-derived cells are antigen-presenting cells and have important roles in immune defense of tissues.

Platelets

Blood platelets are very small non-nucleated, membrane-bound cell fragments only 2 to 4 um in diameter. Platelets originate by separation from the ends of cytoplasmic processes extending from giant polyploid bone marrow cells called megakaryocytes. Platelets promote blood clotting and help repair minor tears or leaks in the wall of small blood vessels, preventing loss of blood from the microvasculature. Circulating platelets have a life span of about 10 days.

A sparse glycocalyx surrounding the platelet plasmalemma is involved in adhesion and activation during blood coagulation. The role of platelets in controlling blood loss and in wound healing can be summarized as follows:

  • Primary aggregation: Disruptions in the microvascular endothelium, which are very common, allow the platelet glycocalyx to adhere to collagen. Thus, a platelet plug is formed as a first step to stop bleeding.
  • Secondary aggregation: Platelets in the plug release a specific adhesive glycoprotein and ADP, which induce further platelet aggregation and increase the size of the platelet plug.
  • Blood coagulation: During platelet aggregation, fibrinogen from plasma, von Willebrand factor and other protein released from the damaged endothelium, and platelet factor 4 from platelet granules promote the sequential interaction of plasma proteins, giving rise to a fibrin polymer that forms a three-dimensional network of fibers trapping red blood cells and more platelets to form a blood clot, or thrombus. Platelet factor 4 is a chemokine for monocytes, neutrophils, and fibroblasts and proliferation of the fibroblasts is stimulated by PDGF.
  • Clot retraction: The clot that initially bulges into the blood vessels lumen contracts slightly because of the interaction of platelet actin and myosin.
  • Clot removal: Protected by the clot, the endothelium and surrounding tunic are restored by new tissue, and the clot is then removed, mainly dissolved by the proteolytic enzyme plasmin, formed continuously through the local action of plasminogen activators from the endothelium on plasminogen from plasma.