Blood

The Blood Rubie Maranan-Causaren, MS

Functions of the Blood: • Transport • Protection – Microorganisms – Blood loss

• Immunity • Aids in maintaining water balance • thermoregulation

General Features: • • • • • •

About 5.5 L in man Components: plasma and formed elements Clotting: coagulum + serum Hematocrit Differential cell count Staining properties

Components of Blood Anticoagulants (heparin, citrate)

Hematocrit (Hct)

(1%)

• Estimate of the volume of packed erythrocytes per unit volume of blood • Normal values – 40%-50% in men – 35%-45% in women

• Diagnosis of anemia and polycythemia (>Hct65)

Four Major Staining Properties: 1. Basophilia • •

An affinity for methylene blue Basophilic structures stain purple to black

2. Azurophilia • • •

An affinity for oxidation products of methylene blue called azures e.g. stains (Giemsa, Wright’s, Leishman’s) Azurophilic structures stain red-blue

3. Eosinophilia or acidophilia • •

An affinity for eosin Acidophilic structures stain yellow-pink to orange

4. Neutrophilia • •

Affinity for complex dyes in the mixture Neutrophilic structures stain salmon pink to lilac

Most abundant α, β, γ; γ includes Ig or antibodies

Converted to fibrin during blood clotting

(Na, K, Ca)

solutes

Figure 34.12b

Red blood cells /erythrocytes

RBCs (a. Normal structure and function) • • • •

size 0.8 µm biconcave Packed with hemoglobin Normal concentration in blood – ~3.9 – 5.5 m/µL in women – ~4.1 – 6.0 m/µL in men

• • • •

flexible mature: non-nucleated mature: no mitochondria mature: lack ribosomes – Limited lifespan: 120 days

• Function?

2.6 µm

7.5 µm

RBCs (b. plasmalemma and stroma) • Plasmalemma: – 40% lipids, 50% proteins, and 10% carbohydrates (antigens)

• Red cell ghost or ghost cells – plasmalemma – Stroma (red cell cytoskeleton)

Stroma Mostly of peripheral proteins Removal? Fragmentation of plasmalemma Functions of stroma? – Biconcave – Strength, elasticity, pliability

Stroma

Integral proteins • Band 3 – Channel (HCO3- and Cl-)

• Glycophorin A – RBCs repel each other – Receptor used by Plasmodium

RBCs (c. hemoglobin) • Interior: 33% solution of hemoglobin (Hb) • Basic protein which accounts for erythrocytes acidophilia • structure

• 1 RBC contains 280 m Hb • O2 + Hb = HbO2 (oxyhemoglobin) • CO2 + Hb = HbCO2 (carbaminohemoglobin) (30%)

ABO Blood Grouping

Type O

Type A

Type B

Type AB

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Rh

Rh Blood Type

WBCs • Shape: amorphous • Migrate to tissues by means of diapedesis – Unidirectional flow of granulocytes & monocytes – Mediated by cell adhesion molecules – Increased during infections and inflammation – A result of chemotaxis • Most die by apoptosis

Figure 35.9

Divisions: Granulocytes • polymorphs • Myeloid cells • include? • two types of granules

• specific granules • azurophilic which stain purple and are actually lysosomes • all are terminal non-dividing cells • few mitochondria (anaerobic glycolysis) • glycogen

Agranulocytes • include? • mononuclear leucocytes • azurophilic granules • non-terminal

WBCs in blood

Blood (WBC) Granulocytes

neutrophil

eosinophil

Agranulocytes

lymphocyte

monocyte

basophil

Differential Leucocyte Count

• Varies according to age, sex, and physiological conditions • Normal adults: 6,000-10,000 WBCs/µL

(Granulocytes)

Neutrophil

• Most common type • Size: 12-15 µm in diameter • Nucleus: – Immature: horseshoe-shaped – Mature: may have 2-5 lobes (usually 3) – Lobulation increases with maturity – Hypersegmented cells – Barr body/drumstick chromosome • Only 3% of neutrophils

(Granulocytes) Cytoplasm:

Neutrophil

Primary granules • 1o? • Actually are azurophilic granules larger than 2o granules • Stain reddish-purple • With maturation, # falls relative to 2o granules • Contain acid hydrolases • Contain myeloperoxidase (antibacterial and digestive) Secondary granules • specific granules about 0.2-0.8 µm • Stain salmon pink • Twice as numerous as 1o granules • Contents are involved with in the mobilization of inflammatory mediators and complement activators which are released during inflammation

Tertiary granules • Recently been described • Contains gelatinase secreted into the extracellular matrix • Also insert some glycoproteins into cell membranes promoting cellular adhesion and hence may be involved in phagocytosis

(Granulocytes)

Neutrophil

• DLC: – 5,000/µL of blood – 60-70% – Normal: 1.5-10 x 109/L – >10 x 109/L (neutrophilia which may indicate bacterial infection or tissue necrosis) – < 1.5 x 109/L (neutropenia which may be due to a decreased production in the bone marrow or to increased destruction in tissues)

• Duration of development: 6-9 days • Lifespan: 6 hours to few days

(Granulocytes)

Neutrophil

Functions: • 1st line of defense against bacterial invasion • Phagocytosis of bacteria and dead cells • Play a central role in the early stages of acute inflammatory response to tissue injury • Defunct neutrophils are the major constituent of pus hence called pus cells • Death: lysosomal enzymes are released in the extracellular space causing liquefaction of adjacent tissue

• opsonization

(Granulocytes)

Eosinophil

• Size: 12-17 µm in diameter • Nucleus: bilobed • Cytoplasm: – Many large (0.5-1.5 µm) specific granules (about 200/cell) that are stained bright red or red-orange • Internum or crystalline core – Contains an extremely alkaline protein called major basic protein (acidophilia) and other proteins • Externum or matrix – Less dense area

(Granulocytes)

Eosinophil

• DLC: – 150/µL of blood – 2-4% – Eosinophilia – associated with allergic reactions (asthma, etc.) and helminthic infestation

• Duration of development: 6-9 days • Lifespan: 8-12 days

(Granulocytes)

Eosinophil

Functions: • Preferentially attracted by substances released from mast cells and basophils, notably histamine and eosinophil chemotactic factor of anaphylaxis (ECF-A), as well as activated lymphocytes (hTL) • Modulate or dampen down allergic reactions – Release of histaminase and aryl sulfatase which inactivate two mast cell products [histamine and slow reactive substance of anaphylaxis (SRS-A)]

• Found in connective tissues underlying epithelia of the skin, lungs, bronchi, GIT, uterus and vagina

(Granulocytes)

Eosinophil

Functions: • Limited phagocytosis of Ag-Ab complexes • Killing of parasites like helminths (mediated by IgE receptors on surfaces of eosinophils) due to release of major basic protein

(major basic protein) IgE

(Granulocytes)

Basophil

• Size: 12-15 µm in diameter • Nucleus: bilobed or S-shaped (3 twisted lobes) but obscured by specific granules • Cytoplasm: specific granules – Large (0.5 µm) IgE – stained metachromatically to reddish-violet to nearly black; IgE receptor deep violet; deep violet-blue – Contain histamine, heparin, SRSA, ECF-A – Contents are released during degranulation (stimulated by an allergen) Mast cell

(Granulocytes)

Basophil

• DLC: – 30/µL of blood – < 1% (0.5%) (least common)

• Duration of development: 3-7 days • Lifespan: hours to days

(Granulocytes)

Basophil

Functions: • Have receptors for IgE produced by plasma cells in response to allergen Exposure to allergen rapid degranulation releasing histamine and other vasoactive mediators

•an immediate hypersensitivity reaction allergic rhinitis (hay fever), some forms of asthma, urticaria, and anaphylaxis

(Agranulocytes)

Lymphocytes

• Size: – 6-8 µm in diameter (small lymphocytes) – 9-18 µm in diameter (large lymphocytes); about 3% of the blood; represents activated lymphocytes

• Nucleus: spherical • Cytoplasm: – Scanty; thin rim around the nucleus – Contains a few azurophilic granules – Few mitochondria – A small golgi complex – Few polyribosomes

(Agranulocytes)

Lymphocyte

• DLC: – 2,400/µL of blood – 28% of circulating blood – Most numerous WBCs in children – Number increases in response to viral infection

• Duration of development: 1-2 days • Lifespan: – 3 days – 20 years – Only WBCs to recirculate after diapedesis

(Agranulocytes)

Lymphocytes (B cells)

Functions: • Migrate into the tissues and special organs of the immune system • “immune surveillance”

(Agranulocytes)

Lymphocytes (B cells) • Types: – *B cells – NK cells – T cells (leave the thymus either CD4+ or CD8+ cells)

*”Bursa of Fabricius”

(Agranulocytes)

Lymphocytes (B cells) • Contains about 150,000 IgM as receptors • Recognize soluble antigens or antigens present on cell surface • Non-terminal (2 main subpopulations): – Plasma cells – Memory B cells

(Agranulocytes)

Lymphocytes (T cells) • Constitute 65-75% of blood lymphocytes • To recognize an epitope, all T cells have TCR (T cell receptor) • Recognize only epitopes the form complexes with MHC of APCs • Non-terminal (2 main subpopulations): – Effector cells • Helper T cell (hTL) or CD4+ T cells • Cytotoxic T cell (cTL) or CD8+ T cells

– Memory cells • Memory Helper T cell • Memory Cytotoxic T cell

(Agranulocytes)

Lymphocytes (helper T cells) • Also called CD4+ cells (CD4 is also used by HIV to enter hTL) • Play a very important role in immune response by: – – – – –

Production and secretion of cytokines Differentiation of B cells to plasma cells Activation of macrophages Activation of cTLs Induction of an inflammatory reaction

(Agranulocytes)

Lymphocytes (cytotoxic T cells) • Also called CD8+ cells • Can act on foreign cells or virus-infected cells by two main mechanisms: – Attach to target cells and release proteins called perforins and results to cell lysis – Attach to target cells and kill them by triggering apoptosis

Lymphocytes (NK cells) • Lack marker molecule characteristic of B and T cells • 10-15% of circulating lymphocytes • Attack virus-infected cells, transplanted cells, and cancer cells without previous stimulation (innate immune response)

(Agranulocytes)

Monocytes

• Size: – 12-20 µm in diameter

• Nucleus: – oval or horseshoe- or kidney- or beanshaped with 2-3 nucleoli

• Cytoplasm: – Basophilic and contains very fine azurophilic granules (lysosomes) – With small quantity of RER, polyribosomes – Many small mitochondria – With golgi complex involved with the formation of lysosomal granules

(Agranulocytes)

Monocyte

• DLC: – 350/µL of blood – 5% of circulating blood

• Duration of development: 2-3 days • Lifespan: – Months to years

(Agranulocytes)

Monocytes

Functions: • Non-terminal cells  mononuclear phagocyte system • macrophages

Platelets

megakaryocyte

• Size: – 2-4 µm (in diameter) disklike fragments arising from megakaryocytes in bone marrow

• Nucleus: non-nucleated • Structure: • Two zones: – Hyalomere – Granulomere • granules, few mitochondria and glycogen

• canalicular system that opens to the external canalicular pits • Marginal bundle – Maintains ovoid shape

• Dense tubular system – Platelet movement and aggregation

• Cell coat (15-20nm thick) – Platelet adhesion

Platelets • Structure: Granulomere (granules): • δ (delta) granules or dense bodies – Contain Ca2+, pyrophosphate, ADP, ATP, and serotonin

• Α (alpha) granules – Contain fibrinogen, platelet-derived growth factor and other platelet-specific proteins

• λ (lamda) granules – Contain lysosomal enzymes

• Number: 300,000/µL of blood – <150 x 109/L (thrombocytopenia) • Duration of development: 4-5 days • Lifespan: 8-12 days • Function: blood clotting

1. Platelet activation

Summary of Blood Clotting

2. Platelet aggregation

Okey na!

RBCs (d. some abnormalities/diseases) • Anisocytosis – Refers to a high % of RBCs with unusually great variations in size – Macrocytes (>9 µm in diameter) – Microcytes (<6 µm in diameter)

RBCs (d. some abnormalities/diseases) • Nuclear fragments – Or Howell-Jolly bodies remain in mature RBCs – When these form circular fragments, they are termed Cabot rings

RBCs (d. some abnormalities/diseases) • reticulocytes – Some RBCs released from the bone marrow contain a small amount of RER and ribosomes – If >1% of circulating RBCs, indicative of an increased demand for oxygen-carrying capacity • From loss of RBCs during hemorrhage or anemia • Recent ascent to a higher altitude

RBCs (d. some abnormalities/diseases)

RBCs (d. some abnormalities/diseases)

Figure 12—4. Scanning electron micrograph of a distorted erythrocyte from a person who is homozygous for the HbS gene (sickle cell disease). x6500.

RBCs (d. some abnormalities/diseases) • Polycythemia or erythrocytosis – >Hct65 – May be a physiological adaptation (in people who live in high altitude with low oxygen tension) – When severe, it can impair circulation of blood through the capillaries

Figure 35.4