Blood belongs to connective tissue and like other types of connective tissues is composed of cells (formed elements) and intercellular matter (plasma).

PLASMA (55-60%) water - 90-93%, organic substances 6-9%, inorganic substances - 1%; the last two include: proteins 60-75 g/l, carbohydrates, lipids, electrolytes

FORMED ELEMENTS (40-45%)

these are subdivided into white blood cells or leucocytes, red blood cells or erythrocytes and platelets or thrombocytes

erythrocytes and platelets perform their functions within the vessel lumen, while leucocytes function primarily in the tissues

shapes:

normal shape: biconcave disc - discocyte

pathological shapes - poikilocytes:

• spherical - spherocytes
• with flat surfaces - planicytes
• with convex surfaces - stomatocytes
• with multiple projections on the cell surface - echinocytes
• with small number of projections -acanthocytes
• bifoveal
• with half disc shape - schistocytes
• sickle-shaped - drepanocytes
• with the shape of a drop - dacryocytes
• resembling a target - codocytes
• perforated in the center, etc..

functions:
transport of oxygen and carbon dioxide, maintenance of blood buffers

PLATELETS

varieties: juvenile, mature, senescent, degenerative and giant

structure:
no nucleus; are pieces of cytoplasm with elements of Golgi complex and smooth endoplasmic reticulum, with mitochondria, ribosomes, glycogen inclusion bodies, microtubules, microfilaments, glycolytic enzymes are present as well as a number of granule types; all elements having a structure of a granule are called granulomere, while all non-granular cytoplasmic components are referred to as hyalomere; there are receptors for blood clotting factors on cytoplasmic membrane

alpha granules contain:

• glycoproteins (fibronectin, fibrinogen, von Willebrand factor), heparin-binding proteins (platelet factor IV: regulates vascular permeability, release of calcium from bone, neutrophil and eosinophil chemotaxis, neutralizes heparin)
• b-thromboglobulin
• growth factors (platelet-derived growth factor, transforming growth factor b)
• clotting factors and thrombospondin (thrombospondin: promotes adhesion and aggregation of platelets; thromboplastin, factor V, GMP-140 - a protein from the selectin family, adhesion receptor)
• there are receptors for coagulation factors on the inner surface of the granule's membrane

delta granules contain: ADP, ATP, calcium ions, serotonin, histamine

lambda granules or azurophilic granules, or lysosomes: (see neutrophils)

microperoxisomes: (see peroxisomes)

properties:
platelets are able to be activated, this process is accompanied by release of granule contents into the intercellular space, and, additionally, inner aspect of granular membrane with receptors for adhesion molecules and coagulation factors on it becomes accessible for inactive clotting factors, which through interaction with these receptors fix to them and then turn activated; platelets are capable of attaching themselves to injured vessel wall (adhesion) and stick to each other (aggregation)

functions:
participation in blood coagulation and thrombus formation

LEUCOCYTES

on the basis of presence or absence of  SPECIFIC granules leucocytes are divided into 2 major group: granular leucocytes (or granulocytes) and nongranular leucocytes (or agranulocytes)

• granulocytes have specific granules, nuclei of mature or nearly mature granulocytes are composed of several segments: they may have two, three or four segments
• agranulocytes do not have specific granules and possess a spherical, oval or horseshoe-shaped nucleus;

granular leucocytes are a heterogeneous group that includes

• basophils
• eosinophils
• neutrophils

• lymphocytes
• monocytes

BASOPHILS

structure:
cells are spherical in shape, in the peripheral blood there are mainly the most mature forms (with segmented nuclei), having, as a rule, a bi-lobed nucleus, their cytoplasm contains specific and nonspecific granules; specific granules stain well with basic (alkaline) dyes; azur-2, a basic dye, has a dark blue color; therefore, staining a blood smear with azur-2-eosin by Giemsa method should turn specific granules of a basophil dark blue; however, due to sulfated proteoglycans within these granules they take a violet-purple tinge, i.e. they show the phenomenon of  metachromasia which is defined as change from the initial color of a dye

specific granule content:

• chondroitin sulfate A (sulfated proteoglycan)
• histamine
• serotonin
• small quantities of neutral proteinases - chymase, tryptase

nonspecific (or azurophilic) granule content: see neutrophils

properties:

• transgression from blood into tissues, migration within tissues
• ability to release granule contents into the extracellular space (degranulation)
• weak phagocytosis
• release of biologically active substances which are not within granules
• uptake of histamine and serotonin from the surrounding tissues (?)

functions:
are determined by versatile actions of granule contents as well as by elaboration and secretion of a host of biologically active substances which are not stored within granules such as tumor necrosis factor a, prostaglandin D2, thromboxane А2, interleukin 4, leukotrien C4 and others

EOSINOPHILS

structure:
cells are spherical in shape, in the peripheral blood there are mainly the most mature forms (with segmented nuclei), having, as a rule, a bi-lobed nucleus, their cytoplasm contains specific and nonspecific granules; specific granules stain well with acidic dyes; eosin, an acidic dye, has red or pink color; therefore, staining a blood smear with azur-2-eosin by Giemsa method should turn specific granules of an eosinophil red or pink; one eosinophil is home to approximately 200 specific granules, on the outer surface of eosinophils there are receptors for IgG, IgE, complement components C3b,C4,C1s, C3a, C5a and others

composition of specific granules:

• major basic (alkaline) protein (damages membranes of parasites and cells, neutralizes heparin and histamine) belongs to cationic proteins
• cationic proteins (forms water channels in membranes which leads to cell lysis)
• peroxidase (destroys hydrogen peroxide with simultaneous release of reactive oxygen species and oxidation of something)
• lisophospholipase (releases from lipids lisolecithin and lisophosphatidylserine which are found in membranes and promote membrane bilayer fusion; lisolecithin can inhibit adenylate cyclase and activate guanylate cyclase; lisolecithin can release from lipids fatty acids such as arachidonic acid)
• histaminase (destroys histamine)
• arylsulfatase B (cleaves sulfate groups)
• phospholipase D (cleaves phospholipids)
• beta-glucuronidase
• collagenase (see neutrophils)
• neurotoxin of eosinophils (leads to death of neurons)

composition of nonspecific (or azurophilic) granules: see neutrophils

properties:

• transgression from blood into tissues and visceral lumina
• migration within tissues and on surfaces of visceral mucous membranes
• ability to release granule contents into the extracellular space (degranulation)
• weak phagocytosis, in which specific granules can fuse with lysosomes and phagosomes, however, this process is not as active as in neutrophils
• ability to attach themselves to parasites (worms), to locally release granule contents and inject into cytoplasm of a parasite

functions:
are determined by actions of granule contents as well as by secretion of a host of biologically active substances which are not stored within granules such as platelet activating factor, thromboxane B2, leukotrien C4 and B4

NEUTROPHILS

structure:
in the blood of a healthy human neutrophils of various degrees of maturity are present: juvenile neutrophils (metamyelocytes) - the youngest, rods - more mature, and segmented neutrophils - the most mature; neutrophils are spherical in shape, in the cytoplasm, in addition to all basic organelles, there are specific (primary and secondary) and nonspecific granules; specific granule content is alkaline or neutral in pH, pH for nonspecific granules is acidic; specific granules stain with both acidic and basic dyes; eosin, an acidic dye, has red or pink color, azur-2, a basic dye, has a dark blue or violet color; therefore, staining with azur-2-eosin by Giemsa method should turn specific granules of a neutrophil brown violet; nuclei of juvenile neutrophils have an indentation on one of their sides, nuclei of rods are horseshoe-shaped, segmented neutrophils have three- or four-lobed, sometimes bilobed; on the outer surface of neutrophils there are receptors for C3b complement component, Fc-receptors for IgG, as well as for many immunologic mediators and other biologically active substances

composition of secondary specific granules:

• cationic proteins (forms water channels in membranes which leads to cell lysis)
• alkaline phosphatase (cleaves phosphates from various substrates, participates in transphosphorylation reactions)
• phagocytin (destroys membranes)
• lactoferrin (deprives proliferating bacteria of iron and iron-containing growth factors)
• vitamin B₁₂-binding protein (binds vitamin B₁₂ necessary for bacterial multiplication)
• lysozyme (destructs peptidoglycans of bacterial cell walls)
• collagenase (cleaves collagen)

composition of primary specific granules:

• myeloperoxidase (catalyses formation of HOCl, which is toxic to bacteria and cells)
• lysozyme (destructs peptidoglycans of bacterial cell walls)
• cationic proteins (forms water channels in membranes which leads to cell lysis)

nonspecific (azurophilic) granules:
(nonspecific granules are lysosomes)

• acid proteinases
• cathepsins A, D, E (cleave proteins, destroy bacteria)
• alpha-fructosidase (releases fructose from disaccharides)
• 5-nucleotidase (releases phosphate from DNA and RNA)
• beta-galactosidase (releases galactose from di- and oligosaccharides)
• arylsulfatase B (cleaves sulfate groups)
• alpha-mannosidase (cleaves mannose from di- and oligo- and polysaccharides)
• N-acetyl-beta-galactosaminidase (cleaves acetylgalactosamines from oligosaccharides)
• beta-glucuronidase (cleaves glycosaminoglycans)
• acid beta-glycerophosphatase (cleaves phosphate from glycerol residue)
• acid phosphatase (cleaves phosphates from various substrates)
• neutral proteinases
• azurocidin (antibacterial protein)
• cathepsin G (cleaves proteins)
• elastase (degrades elastin)
• collagenase (degrades collagen)
• proteinase 3 (myeloblastin) - (degrades elastin)
• cationic proteins (form water channels in membranes, which leads to cell lysis)

properties:

• transgression from blood into tissues, migration within tissues
• directed migration (chemotaxis) into zones of inflammation under the influence of chemotactic factors
• activation by mediators of the immune system and bacteria
• intensive phagocytosis of bacteria and cellular debris (microphagocytosis)
• ability to release their granule contents into surrounding space that causes destruction of tissues and formation of pus
• synthesis of a whole battery of biologically active substances
• during phagocytosis phagocytic vacuole at first fuses with specific granules, then the phagosome-specific-granule complex fuses with nonspecific granules, i.e. lysosomes; therefore, phagocytosed material is first exposed to the actions of specific granule substances, which kills it (bacteria or cells), then lysosome (nonspecific granule) enzymes get into play, which cleave all organic biopolimers down to monomers

functions:
are determined by substances in granules, properties of the cells and by synthesis of multiple biologically active substances

LYMPHOCYTES

structure:
spherical cells with round or slightly indented (in large lymphocytes) nuclei and small cytoplasmic compartment, which contains poorly developed organelles, nonspecific granules (lysosomes) could be seen; morphologically lymphocytes are divided into small, medium, and large lymphocytes; functionally - divided into T- and B-lymphocytes, natural killers, T-lymphocytes are divided in turn into T-killers, T-helpers, T-suppressors, T-memory cells; lymphocytes possess receptors for antigens, immunologic mediators, hormones, and for a host of biologically active substances

properties:

• transgression from blood into tissues, migration within tissues
• directed migration (chemotaxis) into zones of inflammation and immunologic conflicts
• proliferation and differentiation under the influence of various stimuli
• T-killers and natural killers possess cytotoxicity

functions:

• B-lymphocytes transform into plasma cells, which produce antibodies
• T-lymphocytes: T-helpers - facilitate proliferation and differentiation of B- and other T-lymphocytes  (killers, suppressors, memory, natural killers)
• T-killers are cytotoxic, i.e. kill foreign and cancerous cells, viruses, protozoa
• T-suppressors inhibit proliferation and differentiation of T-killers, memory cells, helpers
• T-memory cells store information on antigens getting into the body
• natural killers are cytotoxic against foreign and cancerous cells, viruses, etc.

MONOCYTES

structure:
large round or oval cells with horseshoe-shaped nuclei and quite voluminous cytoplasm, which contains multiple lysosomes (nonspecific granules), phagosomes; cytoplasm stains bluish gray (color of cigar smoke); there are receptors on cytoplasmic membrane for various immunologic mediators, complement components, Fc-receptors for IgG, hormones, biogenic amines, eicosanoids, growth factors, etc.; monocytes are immature cells, than upon leaving the circulation into the tissues, where they differentiate into macrophages

properties:

• transgression from blood vessels into the surrounding tissues or onto mucous membrane surfaces and differentiation into macrophages
• migration in tissues and on surfaces of mucous membranes
• endocytosis
• ability to spread cell body on surfaces
• secretion of multiple biologically active substances
• antigen processing and presentation

functions:

• effector functions - endocytosis, cytotoxicity
• secretion of biologically active substances
• antigen processing and presentation (see macrophage properties)

HEMOGRAM is leucocyte differential count plus concentration of blood cells per liter

AGE-RELATED CHANGES IN BLOOD CELL COUNTS

erytrocytes:6-7*10¹²/l in newborns, get lower post partum and by 10-14 days of life are at adult levels, a decrease continues for 3 to 6 months, then gradual return to adult counts at puberty

leucocytes: 10-30*10⁹/l in neonates, in the first two weeks of life decline to  9-15*10⁹/l, reach adult levels at puberty

neutrophil/lymphocyte ratio: at birth - comparable to adults, 4 days - concentrations equalize, and then lymphocyte counts rise through the age of 1-2 years, after that decline and turn even at 4 years, before puberty neutrophils rise and lymphocytes drop