Blood


 * 24 August 2006**
 * Blood**
 * Dr. Joana Chakraborty, Ph.D.**

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=**Blood**=


 * Functions include: [|respiration], nutrition, excretion, acid-base balance, water balance, body temperature, immune defense, hormone and metabolite transport, and [|coagulation]
 * **6%-8% of total body weight**
 * **Total volume approximately 5.5 L** (6 quarts)
 * **Total RBC volume** 0.45 x 5.5 L = **2.5 L**
 * i.e. RBC volume is 45% of total volume
 * **Total plasma volume** 5.5 L – 2.5L = **3 L**
 * Remaining “liquid” portion of the blood

**Plasma and Serum**

 * **Plasma is 93% water** with 7% dissolved substances
 * Contains proteins: [|albumins], globulins, and [|clotting factors]
 * Electrolytes, nutrients (glucose, amino acids, lipids, cholesterol, vitamins), waste products (urea, [|creatinine], [|bilirubin]), hormones
 * **[|Plasma]** = serum **+** [|fibrinogen] and other clotting proteins
 * Can be separated by centrifugation of whole blood, leaving plasma as supernatant
 * **Serum** = plasma **–** fibrinogen and clotting proteins
 * Plasma supernatant can be left overnight to settle to separating fibrogen and clotting factors, leaving serum as supernatant
 * Plasma is needed to determine fibrogen and clotting factors because serum does not have either.

**Cellular Components of Blood**

 * [|Erythrocytes] (a.k.a. RBCs)
 * [|Leukocytes] (a.k.a. WBCs)
 * [|Thrombocytes] (a.k.a. Platelets)

=**Red Blood Cells**=


 * Biconcave, reversible deformity
 * No mature human RBCs have nuclei or any organelles
 * Presence of immature RBCs which retain nuclei is a bad sign
 * Contains only hemoglobin
 * Oxygen-carrying protein
 * **120 day lifespan**
 * Must be replaced by new cells
 * 90% of RBC dry weight

**Adult Reference Ranges for RBCs**

 * Average concentration of hemoglobin:
 * **13.6-17.2 g/dl in men**
 * **12.0-15.0 g/dl in women**
 * Average erythrocyte count:
 * **4.3-5.9 x 106/mm3 in men**
 * **3.5-5.0 x 106/mm3 in women**

**Laboratory Studies**

 * Obtain blood sample using [|venipuncture]
 * Use vacutainers, syringes
 * Know each lab study to be performed
 * Identify additives and additive function, in color-coded top tubes
 * Precaution for [|HIV], [|hepatitis B], [|hepatitis C], and other blood borne infections
 * Be **very** careful and don’t stick yourself
 * Odds of seroconversion for HIV have been published as 400:1, but that's still significant

**Hematocrit**

 * [|Hematocrit] is the estimation of packed erythrocytes per unit volume in blood
 * Normal volumes:
 * **Men: 40%-50%**
 * **Women: 35%-45%**
 * Container: **Purple top** evacuated tube
 * Contains EDTA anticoagulant
 * Collection: routine venipuncture; invert tube gently
 * Store at 4°C
 * Rejection if clotted or hemolyzed
 * To measure [|hemoglobin], follow same procedure but do not add EDTA.
 * Hemoglobin abbreviated as Hg and Hgb
 * Hemoglobin determines the oxygen carrying capacity while hematocrit only determines the RBC volume
 * Hematocrit is also predictive of hemoglobin content but a hemoglobin test would be more accurate

**Spectrin**

 * Human RBC membrane protein – long fibrous molecule with two polypeptide chains
 * Interacts with actin and forms a fuzzy coat inside RBC membrane
 * Allows RBC to deform as necessary, and responsible for overall stability of RBC membrane
 * [|Hereditary Spherocytosis] – lack of [|spectrin], resulting in RBCs lacking deforming ability
 * Cause blood to hemolyze when they get stuck in capillaries in the spleen and people to become anemic

=**White Blood Cells**=


 * WBCs are 7,000 per mm3 of blood versus RBCs with 5,000,000 per mm3 of blood
 * Also called [|Leukocytes] and have 2 types:
 * [|Granulocytes] – contain granules
 * [|Neutrophils] – does not show up on either acidic or basic stains
 * [|Eosinophils] – show up on acidic stains
 * [|Basophils] – show up on basic stains
 * Agranulocytes – no granules
 * [|Lymphocytes] – 20-40% of all leukocytes
 * [|T lymphocytes]
 * [|B Lymphocytes]
 * [|Monocytes]

**Neutrophil**

 * Most of WBCs and have multilobed nuclui 50-70%
 * They are phagoctyes and sometimes called microphages
 * **If there is a bacteria infection, neutrophils will be abundant**
 * Bacteria destroyed in connective tissue spaces
 * Contains specific granules
 * In females, the inactive X chromosome appears as a drumstick-like appendage on one of the nuclear lobes

**Eosinophils**

 * Few in number 1-4%
 * Have a **bilobed nucleus**
 * Important for allergic reaction and **[|parasitic worm] killing**
 * Granules contain a crystalline core and a less dense matrix

**Basophil**

 * Few in number <1%
 * S-shaped nucleus with large granules in cytoplasm
 * Acts as an initiator in the [|inflammatory process]

**Monocytes**

 * Largest cells in circulatory blood
 * 2-8% of total leukocytes
 * When they enter connective tissue space, they are called [|macrophages]
 * In circulation, they are monocytes
 * Produce cytokines and can present antigen to T-cells

=**Thrombocytes**=
 * 250,00 per mm3 of blood
 * Also called platelets
 * Contains no nucleus but have organelles
 * Originate from the fragmentation of the cytoplasm of giant [|megakaryocytes] in the [|bone marrow]
 * In peripheral area of platelets, there are lots of microtubules that act to get granules into the right place
 * During coagulation, the platlet membrane invaginates to connect to the open canalicular system, which contains the 4 granules responsible for the clotting process
 * Two Granules include:
 * serotonin --> acts as a vasoconstrictor
 * Platelet-derived growth factor --> stimulates endothelial cell mitosis

=**Hemopoiesis**=


 * Hemato means “blood,” poiein means “to make”
 * [|Erythropoiesis] – for RBCs
 * Granulopoiesis – for granulocytes
 * Monocytopoiesis – for monocytes
 * Megakaryocytopoies – for megakaryocytes

**Pluripotential Hematopoietic Stem Cells**

 * [|Pluripotential Hematopoietic Stem Cells] produce of all types of blood cells
 * Abbreviated PHSCs
 * Pluripotential – potential to differentiated into any blood cell
 * Divide continuously
 * Daughter cells are irreversibly differentiated
 * Produce two types of multipotential hematopoietic stem cells (MHSC):
 * Colony-forming unit-spleen (CFU-S) – myeloid cell line
 * Colony-forming unit lymphocytes (CFU-Ly) – lymphoid cell line

**Progenitor Cells**

 * Progenitor cells are daughter cells of MHSC
 * Mitotic activity and differentiation are controlled by specific hematopoietic factors
 * Limited capacity of self-renewal
 * Can undergo mitosis but cannot undifferentiated back to a [|PHSC]

**Precursor Cells**

 * Produced by progenitor cells
 * No self-renewal capability
 * Undergo cell division and differentiation
 * Produce clones of mature cells
 * Each precursor cell has a unipotential colony-forming unit

**Hematopoietic Growth Factors**

 * Determines differentiation of progenitor cells
 * [|Erythropoietin] – makes erythrocytes
 * [|Colony-stimulating factors] – Granulocytes and monocytes
 * [|Interleukins] – various leukocytes
 * Throbopoietin – platelets
 * Stem cell factor – many types of blood cells

=**Granulocytes **=


 * Colony-forming unit lymphocytes (CFU-Ly) form Myeloblast
 * Myeloblast forms promyelocytes
 * Promyelocytes produce:
 * Neurtrophilic Myelocyte
 * Eosinophilic Myelocyte
 * Basophilic Myelocyte

**B-Lymphocytes**

 * Produced from the bone marrow and can go directly to lymph nodes or spleen
 * [|Humoral immunity]
 * Activated [|B lymphocytes] produce [|plasma cells] which actively produce antibodies specific to an antigen
 * Antibodies circulate throughout the body via blood and lymph
 * Do not interact with [|MHC] proteins and can recognize [|antigen] on their own

**Humoral Immunity**

 * [|Plasma cells] produce antibodies which are called [|immunoglobulins] (Ig)
 * Five-classes of Ig depending on the antigen that they have
 * **[|IgG] – 80%**
 * Immunity against bacteria and viruses in the extracellular fluid
 * [|IgM] – 5%
 * Immunity against bacteria and viruses in the extracellular fluid
 * [|IgA] – 15%
 * Secreated by plasma cells in GI, respiratory, genitourinary tracts, and [|breast milk]
 * Babies lack a lot of antibodies after birth and get their IgA from their mother’s milk
 * However, women infected with HIV can pass HIV to babies through breast milk
 * [|IgD] – <1%
 * Function not clear
 * [|IgE] – <1%
 * Defense again multicellular parasite and allergic reaction

**Antibody Structure**

 * Have heavy and light chain
 * Variable region of antibody allow of antibody specificity

**T-Lymphocytes**

 * [|Cell-mediated immunity]
 * Produced in [|bone marrow]
 * Requires antigen presentation via [|major histocompatibility complex II] (MHC) restriction
 * B cells can recognize antigen, but T-cells need presentation
 * Migrated to the thymus before going to lymph nodes or spleen
 * Three different types:
 * [|T helper cells] (TH1 and TH2)
 * [|Cytotoxic T cells]
 * [|T memory cells]
 * ([|Regulatory T cells] - not mentioned in lecture)

**Antigen Presentation**

 * Marcophage must present antigen to T cells
 * [|Helper T cell] can bind with presented antigen on [|MHC-II]
 * [|MHC-II] is found only on macrophages, macrophage-like cells, and B cells
 * Interacts with Helper T cells
 * [|MHC-I] is found on all nucleated cells in the body
 * Interacts on [|cytotoxic T cells]

=**Roles of B cells, Cytotoxic T cells, and Helper T cells in Immune Response**=


 * [|B cells] when activated become [|plasma cells] and produce antibodies to guide [|phagocytes], [|complement], and [|NK cells] to attack antigen-bearing cells or neutralize free antigen
 * [|Cytotoxic T cells] directly attack antigen bearing cells
 * [|Helper T cells] produce [|cytokines] upon antigen exposure which help promote [|B cells] to turn into [|plasma cells] and make [|Cytotoxic T cells] more competent
 * [|Helper T cells] have a key role in immune response
 * HIV destroy T cells, especially [|Helper T cells] and severely inhibit [|immune response]

=**Objectives**=