Unit III- Peripheral Blood Flashcards
General characteristics of blood
- specialized form of CT
- enclosed in blood vessels and flows through body (about 5 liters)
- exchange of materials between blood and surrounding tissues
- cooperates with nervous and endocrine systems to integrate and regulate bodily functions
Blood components
- formed elements (erythrocytes (red blood cells), leukocytes (white blood cells) and platelets)
- plasma- aqueous solution containing large and small molecular weight substances and proteins
Proteins in blood plasma
- albumin is the major component-maintains osmotic pressure of the blood, plays a role in transport of water insoluble substances
- gamma globulins (immunoglobuluns)- antibodies
- fibrinogen- necessary for formation of fibrin during blood clotting
- complement proteins- important in inflammation and destruction of microorganisms
- other solutes- electrolytes such as Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, PO43-, SO421; non-protein
Centrifugation- lowest layer
1) Consists of red blood cells
2) Represents about 45% of blood volume
a) 41% for females
b) 45% for males
3) Hematocrit
a) Percentage of blood volume occupied by red blood cells
Centrifugation- middle layer (buffy coat)
1) Represents about 1% of blood volume
2) White or gray in color
3) Consists of leukocytes and platelets
a) lymphocytes
b) monocytes
c) neutrophils
d) eosinophils
e) basophils
Centrifugation- upper layer
1) Blood plasma
2) Slightly more than 50% of blood volume
3) Yellowish translucent supernatant
Formed elements
erythrocyes, leukocytes, platelets
Erythrocytes
Structure at light microscope level:
-biconcave discs without nuclei, diameter: 6.5-8.0um, bind eosin deeply around periphery
Ultrastructure:
-plasma membrane:
trilaminar, membrane skeleton: network of peripheral proteins, attached to cytoplasmic side of lipid bilayer, composed largely of spectrin, actin and protein 4.1, influence deformability of membrane, stabilize membrane against shearing forces
-lack nuclei, ribosomes, mitochondria, ER, Golgi and lysosomes
Factors influencing the ability of erythrocytes to change shape
- in order to pass through capillaries
- their geometry (biconcave disc)
- cytoplasmic viscosity (intracellular hemoglobin concentration)
- properties of their plasma membrane
Hemoglobin
- 1/3 of cell weight
- responsible for cytoplasmic viscosity and eosinophilia
- globular chromoprotein- a tetramer consisting of 4 globin polypeptide chains, each polypeptide chain is associated with a heme group- each heme group is a protoporphyrin associate with iron
Types of hemoglobin
Hemoglobin A1- major form of hemoglobin in adults (95%), consists of 2 alpha polypeptide chains and 2 beta polypeptide chains
Hemoglobin A2- minor form of hemoglobin in adults (5%), consists of 2 alpha and 2 delta
Hemoglobin F- produced during the intrauterine period, consists of 2 alpha and 2 gamma
Hemoglobin S- single nucleotide mutation in DNA coding for beta polypeptide chain (glutamic acid to valine), leads to sickle cell disease- rbc are inflexible and have reduced life span, can lead to anemia, can increase blood viscosity
Function of red blood cells
transportation of gases
- oxygen from pulmonary alveoli to tissues (oxyhemoglobin)
- carbon dioxide from tissues to pulmonary alveoli (carbaminohemoglobin)
Number of red blood cells
males: 4.1 x 10^6/ ul (5.1)
females: 3.9-5.5 x 10^6/ul (4.5)
influenced by altitude
Life span of red blood cells
- survive in circulation for about 120 days
- senescent red blood cells are removed by macrophages (spleen, liver, bone marrow)
Reticulocytes
- red blood cells recently released from bone marrow
- contain small amount of ribosomal RNA- stains with brillant cresyl blue, appears as a net-like cytoplasmic structure
- make up about 1% of total number of circulating erythrocytes
- useful indicator of rate of erythrocyte production:
1) diagnosis and classification of anemias
2) monitoring treatment of anemia
3) monitoring bone marrow regeneration
4) monitoring hemopoietic restoration after erythropoietin therapy
Leukocyte Classification
Granular leukoctyes: (have specific cytoplasmic granules)
- neutrophils (PMNs)
- eosinophils
- basophils
Agranular leukocytes (lack specific cytoplasmic granules)
- lymphocytes
- monocytes
Leukocyte function out blood vessels
- leave vessels by means of diapedesis
1) between cells
2) through cells
Number of leukocytes
6000-10,000/ul (7,500) relative frequency: -neutrophil 60-70% -eosinophil 2-4% -basophil 0-1% -lymphocytes 20-30% -monocytes 3-8%
Neutrophil structure at light microscope level
- 12-15 um in diameter
- nucleus consists of 2-5 lobes (polymorphonuclear)
- nucleus is heterochromatic
- no nucleoli
- cytoplasmic granules
a) specific granules (secondary, definitive, neutrophilic) - very small, responsible for staining qualities of cytoplasm (salmon pink), 80% of granule population, have specific functions
b) azurophilic granules (primary) - large, stain with Azure B, primary lysosomes
Ultrastructure
1) nucleus- heterochromatic
2) cytoplasmic- a few mitochondria, small Golgi complex, poorly developed RER, few free ribosomes, considerable glycogen
Functions of neutrophils
- Phagocytosis
a) neutrophils are motile
b) neutrophils display chemotaxis
c) pseudopodia surround bacteria forming phagosomes
d) specific granules fuse with phagosome
e) specific granules discharge their contents into phagosome- lysozyme hydrolyzes glycosides in bacterial cell wall, lactoferrin is an iron binding protein
f) azurophilic granules fuse with phagosome forming secondary lysosome- enzymes hydrolyze dead bacterium into its constituent small molecules - formation of superoxide (O2) anions
- netosis: release of a net-like structure capable of trapping microbes
- neutrophils die during these processes forming pus
- production of cytokines (TNFalpha, IL-1B, IL-8, TGF-B1)
Eosinophils- structure
-2-4% leukocytes structure at light microscope level: -12-15 um in aidmeter -nucleus is bilobed -large eosinophil specific cytoplasmic granules (no azurophilic
ultrastructure:
-cytoplasmic granules are their most striking feature-granules have a crystalline core (major basic protein) also contain hydrolytic enzymes
Functions of eosinophils
- kill the larvae of parasitic worms (major basic protein)
- phagocytosis of antigen-antibody complexes
- inactivate mediators of inflammation (histamine and SRS-A)
- synthesize lipid mediators of inflammation (leukotrienes)
- produce a variety of cytokines (ILs 3,5,6,8,12)
- play a role in asthma (infiltrate bronchial mucosa): broncoconstriction, excess mucus secretion, inflammation, airway remodeling (hyper-responsiveness, increased smooth muscle, increased collagen in ECM, goblet cell metaplasia)
Structure of basophils
Structure at light microscope level:
- 12-15 um in diameter
- nuclei are less segmented than neutrophils or eosinophils
- nucleus usually obscured by cytoplasmic granules that stain intensely with Azure B- azurophilic
Ultrastructure:
- cytoplasmic granules are most striking feature
- have a lamellar or spherical substructure
- granules are rich in heparin, histamine and SRS-A
Function of basophils
- play a role in inflammation (generalized response)
- immediate hypersensitivity reactions (localized or wide spread, mediated by IgE)
- delayed hypersensitivity reactions (take 12-18 hrs to develop
- in many clinical situations basophils and eosinophils accumulate at the same site
Small lymphocytes
- intensely staining spherical nucleus
- thin rim of cytoplasm
- 6-8 um diameter
- most frequent size in peripheral blood
Medium lymphocyte
- larger and less heterochromatic nucleus
- more abundant cytoplasm
- 8-10 um in diameter
Large lymphocyte
- cells activated by specific antigens
- more diffuse nucleus
- cytoplasm contains more organelles
- 10-18 um in diamter
- some large lymphocytes have azurophilic cytoplasmic granules
Function of B lymphocytes
- humoral immunity
- 10-15% of circulating lymphocytes
- differentiate into plasma cells which produce antibodies (immunoglobulins)
- have immunoglobulin molecules on their cell surface (antigen receptors)
- undergo mitosis in response to antigenic stimulation- some daughter cells diffferentiate into antibody producing plasma cells, some differentiate into memory B cells that are primed to respond more rapidly to subsequent exposure to specific antigen
3 size classes of lymphocytes
- small medium
- large agranular
- large granular
Function of T lymphocytes
- cell-mediated immunity
- 70-80% of circulating lymphocytes
- T cell receptors are not immunoglobulins
- T cells require antigen presenting cels
- some activated T cells differentiate into cytotoxic T cells (CD8+): cell mediated immunity (perforin and granzymes)
- some activated T cells differentiate into helper (CD4+) and regulator (suppressor) T cells
Regulator T cells
- suppress the response of other leukocytes to foreign antigens
- they may also suppress immune responses to self antigens (protect against autoimmune diseases)
- they may block antitumor responses of cytotoxic T cells
Natural Killer (NK) cells
- about 5% of circulating lymphocytes
- have neither B nor T cell surface molecules
- have large azurophil granules
NK functions
- kill virus infected cells
- kill malignant cells
- production of cytokines (interferon-gamma) that influence host’s immune response- t cell polarization, maturation of dendritic cells
Monocyte structure
- about 4% of circulating leukocytes
- morphology at light microscope level:
- 12-20um in diameter
- variable shaped, euchromatic nucleus
- abundant cytoplasm that contains numerous azurophilic small granules and vacuoles
ultrastructure:
-nucleolus often observable, full complement of cytoplasmic organelles
Monocyte/ macrophages
- phagocytosis of bacteria and tissue debris
- concentrate and process certain antigens for presentation to lymphocytes (antigen presenting cells)
- formation of osteoclasts
- formation of giant cells in cases of chronic inflammation
- production of cytokines that are involved in the regulation of hematopoiesis
- immune surveillance of endothelial cells (patrolling???)
Morphology of platelets
- small cytoplasmic fragments of megakaryocytes
- 2-4um in diameter
- non-nucleated
- central darkly staining granulomere
- peripheral less intensely staining hyalomere
- usually appears in clumps
- normal platelet count: 250,000/ ul
- average life span: 10 days, die by apoptosis
- contain a functional repertoire of mRNAs
Functions of Blood Platelets
- seal off small breaks in blood vessels (platelet plug)
- role in blood coagulation (provide a surface and produce factors 8 and 9)
- maintain competence (integrity) of endothelium
- role in inflammation associated with rheumatoid arthritis (may increase vascular permeability thorugh release of serotonin??)
- may inhibit angiogenesis and tumor growth by releasing thrombospondin-1??
