physio script #13 ( serum & RBC"s )

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    Components of the blood

    The blood in general is composed of plasma and cells, the plasma itself is composed

    mainly of water and we can find a lot of elements in the plasma like hormones,

    enzymes,plasma proteins, electrolytes or gases. All these things are dissolved orcarried in the blood either by being dissolved or carried by the plasma protein and

    we can find the cells like erythrocytes, leucocytes and platelets.

    So blood is composed mainly of plasma and formed elements, which we are going

    to study. We are going to concentrate on the physical characteristic of the blood, its

    functions and the viscosity of both the blood and lymph.

    So as seen in slide 2; this is a sample of blood, which is venous, if it is spun in a

    centrifuge, the heavier formed elements are packed down by centrifugal force and

    the less dense plasma remains at the top, so if we take a sample of venous blood and if

    we centrifuge it the dense/heavy elements of the blood (cells) will stay at the bottom

    and plasma will go upwards.

    PlasmaThe plasma has 2 components:

    1) cellular components (formed elements) which includes erythrocytes2) the Buffy coat which is a whitish layer present at the site of the erythrocyte plasma

    and it containsLeukocytes andplatelets.

    We also have liquid components (plasma) which makes about 55% of the blood

    making the cells about 45% of the blood.

    Erythrocytes normally constitute 45% of the total volume of blood. This percentage is

    known as the hematocritSO THE CELLS IN THIS PERCENTAGE ARE

    KNOWN AS THE HEMATOCRIT-. In males and females, this percentage might

    differ:

    IMPORTANT: (in males: 45- 47% 5% , in females: 40-45% 5% )

    Plasma is the fluid portion of the blood which contains proteins which are the most

    important component of blood (albumins, globulins, and fibrinogens) these are the

    plasma proteins and we can also find in the plasma nutrients, metabolic end products,

    hormones, and mineral electrolytes.

    Plasma is obtained when unclotted blood is centrifuged. The fluid which rises above

    the cellular elements is in fact the PLASMA.

    Serum is plasma from which fibrinogen and other coagulation proteins have

    been removed as a result of clotting. It contains high level ofserotonin(released from platelets during clotting). It is obtained when clotted blood is

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    centrifuged. The fluid above clotted blood is SERUM i.e. Serum is the liquid part of

    the blood after the coagulation.

    .

    These are cellular elements in cell; they includeplatelets, Erythrocytes, different

    types of leukocytes and the subtypes of leukocytes -1- granule -2- Agranule cytes.

    The total plasma protein is 7-8 g/dl

    Albumin about 4.5 g/dl

    Globulin about 2.5 g/dl (alpha, beta and gamma globulins)

    Fibrinogen about 0.3 g/dl

    {Its important to know the amount of each protein}.

    Most plasma proteins are produced by the liver, except for hormones and gamma

    globulins (they are formed by plasma cells). Being 8% by weight of plasma

    volume, plasma proteins serve a variety of functions, but they are not taken up bycells to be used as fuels or metabolic nutrients as are most other plasma solutes, such

    as Glucose,fatty acids, andamino acids.

    HypoproteinemiaHypoproteinemia is seen in:

    a. liver disease(low production of protein- less formation-)

    b. kidney diseases(loss of protein) such asNephritic syndrome you find signs

    which are protein urea-means protein uric-

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    In the liver hypoproteinemia; decreases the concentration of protein in blood.

    Albumin: MW= 69000

    It Accounts for about 60% of plasma protein

    It acts as a carrier of many substances in the circulation,

    It is an important bloodbuffer and the major bloodprotein contributing to the

    ONCOTIC PRESSURE (plasma osmotic pressure).

    This pressure helps to keep water in the bloodstream.

    Globulins ( and ) act as enzymes and carriers.

    - They are produced by the liver.

    - Antibodies (gamma globulins, immunoglobulin) produced by plasma cells.

    - Fibrinogen produced by liver forms fibrin threads of blood clot.

    In the plasma we have:

    nutrients and hormones and the difference between hormones and enzyme is that:

    {hormones are secreted from specific organs and effects in the body directly, forexample: antidiuretic hormone (ADH)secreted from the hypothalamus it acts

    on the connecting tubules in the kidney}.

    {enzymes are secreted from one organ and acts locally in that organ, for example :

    pepsinit is secreted from the stomach it acts locally in the stomach }.

    Electrolytes; Ca++

    , K+, Cl

    -, HCO3

    -, Na

    +ions help to maintain the osmotic pressure.

    Sodium ions are the major solute contributing to blood osmotic pressure and they helpin maintaining a normal blood pH.

    (Normal pH is 7.35 or 7.45) it is a trump.

    Above 7.45 we call it alkalosis

    Below 7.35 we call it acidosis

    - its danger leads to death that's why it is extremely important for patients to

    get intensive per units of ABG (arterial blood gases) and they should be taking it

    hourly in order to check if theyre blood is in the state of acidosis or alkalosis.

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    We have 2 types of acidosis and alkalosis 1) We have metabolic acidosis or alkalosis

    2) respiratory acidosis or alkalosis (the function of the respiratory system is in the acid

    base balance, it is the moment to moment control of acid base balance determined by

    CO2 or O2).

    ***when we study the GI we can ask about metabolic acidosis or alkalosis but once

    we study the respiratory system we have to know by heart the respiratory acidosis and

    alkalosis.***

    The formula that makes a difference between acidosis and alkalosis is that when the is

    shift in the hemoglobin-oxygen dissociation is curved to the right

    It increases CO2

    It increases the H ions which is the product of metabolism

    It increases the temperature.

    It increases 2,3 bisphosphoglycerate, all these factors shift the curve to the right.

    Physical Characteristics and Volume:

    Total blood volume: 8% of body weight, slightly alkaline pH between 7.35 and

    7.45.

    -Blood is denser than water and about 3-4 times more viscous. Why? Because of the

    cells (cell components).

    Blood functions:

    There are six functions:

    1) Transportation

    O2lungs cells

    CO2cells lungs

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    -The formed elements are present in the buffy coat and the bottom red layer (RBCs,

    WBCs and platelets).

    -Erythrocytes have no nuclei or organelles and the platelets are cell fragments. Only

    the leukocytes are true cells.

    -Erythrocytes and platelets do not divide.

    Blood viscosity:

    It is Plasma protein, the main component of blood elements and is what sets the

    principle of the blood viscosity. Viscosity is increased when hematocrit value or

    Number of RBCs rise.

    Erythrocytes

    Plasma membrane is in an enclosed sac full of hemoglobin

    (thats why they are called Bags of hemoglobin) with no

    nucleus or organelles.

    *whats the importance of RBCs ???

    It contains hemoglobin which is responsible for the transfer of

    oxygen (mainly), and at a lesser rate carbon dioxide and

    hydrogen ions.

    *Structural characteristics:

    1) Small, biconcave shape which provides a large surface area for diffusion of oxygen

    molecules across the membrane.

    2) Concentration; in females 4.7-5 million per cubic mm, in Males 5.2-5.5 million per

    cubic mm

    3) Lacks nucleus; life span = 120 days

    4) Thickness; 2.5/1 so oxygen can diffuse rapidly between exterior and innermost

    regions of the cell

    5) Relay on glycolysis for ATP production (not on oxidative phophorylation because

    it has no mitochondria)

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    *RBC Production:

    1) During early weeks of pregnancyproduction of primitive nucleated RBCs in

    yolk sac

    (Wikipedia:- yolk sac: membrane sac attached to an embryo providing early

    nourishment in the form of a yolk)

    2) During the middle trimesterproduction of RBCs from the liver (mainly), spleen

    and lymph nodes

    (Wikipedia:- first trimester= months 1-3 of pregnancy, middle trimester= months

    4-6, third trimester= months 7-9)

    3) During the last month of pregnancy and after birth (0-5years)all from the bone

    marrow.

    4) 5-10 years from the shaft of long bones (then it becomes fatty and its

    contribution in forming RBCs is reduced gradually and eventually stops completelyafter 20 years. The heads of long bones however, continue to form RBCs )

    5) >20 years almost all in membranous bones.

    *Relative rates of RBC production in bone marrow of different bones at different

    ages.

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    Hemoglobin

    *Parts:

    1) Globin Protein four highly folded polypeptide chains

    2) Four iron containing non protein groups (heme groups), each can combine

    reversibly with one oxygen molecule, thus each hemoglobin molecule binds with 4

    oxygen molecules.

    - The relationship between hemoglobin and oxygen is reversible (hemoglobin binds

    oxygen and release it to tissues)

    *Role:

    1) Transfer oxygen molecule and carbon dioxide molecules

    2) Buffer capacity

    * Average values of hb:

    Adult males 16 g/100ml

    Adult females 14 g/100ml

    Erythropoiesis

    *Erythropoiesis: RBCs Production (because RBCs cant divide, the old ruptured

    cells must be replaced by new cells produced in bone marrow). Although the various

    formed elements have different function, they all arise from the same stem cell.

    1) In children, most bones are filled with red bone marrow that is capable of blood

    cell productions. Red bone marrow is the ultimate source for leukocytes and platelets

    as well.

    2) As a person matures,however, fatty yellow bone marrow that is incapable of

    erythropoiesisgradually replaces red marrow, which remains only ina few isolated

    places, such as the sternum (breastbone), ribs,and upper ends of the long limb bones.

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    * Pluripotent hematopoietic stem cell (PHSC):

    -The 'mother of all cells'the progenitor of all hematopoietic cellse.g. platelets,

    RBCs, neutrophils, macrophages, lymphocytes.

    -Derived from mesenchymeonce committed it follows its path.

    *PHSC gives:

    1. Committed stem cells that produce RBC, granulocytes, monocytes , platelets

    2. Committed stem cells that give lymphocytes

    3. PHSC that keeps a supply of committed stem cells

    *Notes:1) growth inducers like interleukin-3 makes PHSC to give different committed stem

    cells.

    2) Differentiation of different colonies into different blood cells is done by different

    inducers

    3) Erythropoiesis begins when a stem cell is transformed into a proerythroblast

    (committed cell)

    Committedstem cell thatform RBC,Granulocytes,monocytes,platelets

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    RBCs Maturation Stages

    Time needed for committed stem cells to develop to mature erythrocytes is about 5-7

    days.

    1) Proerythroblast: is the first cell belonging to the red blood series.

    2) Early Erythroblast: (ribosome synthesis) little of Hb starts to accumulate

    3) Late Erythroblast: (hb accumulation) Hb concentration is increased until it forms

    almost 34% of volume of the cell.

    4) Normoblast: (ejection of nucleus)

    5) Reticulocyte: Very few Hb is formed. It is the last stage which does not contain

    nucleus and the cytoplasmic organelles are disappearing and the only remnants of

    these remained. They leave the bone marrow and stay in the blood for 1-2 days and

    finally they form mature RBC. Normal reticulocytes number in circulation is about

    1% of total RBC number

    6) Mature Erythrocyte

    Erythropoiesis control* low O2 levels do not stimulate erythropoiesis by acting directly onthe red bonemarrow. Instead, it reduces O2 delivery to the kidneys,stimulates them to secrete thehormone erythropoietininto the blood and this hormone in turn stimulateserythropoiesisby the bone marrow.

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    *Erythropoietin (EPO):A hormone produced mainly by tubular epithelial cells in

    the kidney (90%) and hepatocytes in liver (10%) that promotes the formation of red

    blood cells in the bone marrow. EPO is a glycoprotein (a protein with a sugar attached

    to it). Human EPO has a molecular weight of 34,000.

    1) Stimulus: A drop in normal oxygen levels (hypoxia) triggers erythropoietin

    formation. Hypoxia is the most potent stimulus for erythropoietin production. Other

    factors that increase erythropoietin production are Androgen, alkalosis and

    Catacholamines.

    2) When less O2 is delivered to the kidneys, they secrete the hormone erythropoietin

    into the blood.

    3) Erythropoietin stimulates erythropoiesis (erythrocyte production) by the bone

    marrow

    4) The additional circulating erythrocytes increase the O2-carrying capacity of the

    blood.

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    Fragile Membrane

    Cells Rupture as they pass through

    narrow spaces in spleen

    5) The increased O2-carrying capacity relieves the initial stimulus that triggered

    erythropoietin secretion.

    Destruction of Erythrocytes

    The anucleated condition of erythrocytes carries with it some important limitations.

    -Red blood cells are unable to synthesize new proteins, to grow, or to divide.

    -Erythrocytes become old as they lose their flexibility and become increasingly

    rigid and fragile, and their contained hemoglobin begins to degenerate.

    -Aged RBCs have:

    Metabolic activity

    Enzyme activity

    ATP

    Membrane Lipids

    *Process:

    1) In the red pulp of the spleen, RBC rupture when they try to squeeze through

    because of their fragile old membrane.For this reason, the spleen is sometimes calledthe red blood cell graveyard.

    2) Macrophages in spleen, liver and red bone marrow phagocytize dying RBC.

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    -Globinbreaks into amino acids, which can be reused to produce other proteins

    -Hemeiron and porphyrin

    -Fe removed and recycled in spleen

    -Porphyrinconverted to bilirubin (bile pigment)

    Yellow pigment secreted by liver into bile, which is excreted in urine and feces

    Diseases of Red Blood Cell

    Anemia :

    *Definition; a decrease in the number of red blood cells (RBCs) (less than the normal

    quantity of hemoglobin in the blood). However, it can include decreased oxygen-

    binding ability of each hemoglobin molecule.

    *Causes:

    1) Insufficient number of RBC

    2) Low hemoglobin content

    3) Abnormal hemoglobin

    *Effects:

    anemia

    Decreased

    viscosity

    Decreased

    resistance to

    blood flow

    hypoxiaDilatation of

    blood vessels

    More blood

    returns to the

    heart

    More cardiac output

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    Polycythemia Lea

    Blood volume

    Hematocrit

    viscosity

    decreased blood flow Increased blood pressure

    Decreased venous

    return to the heart

    Decreased cardiac output

    Increased

    venous return

    Increased cardiac

    output

    More O2 is extracted from Hb and

    thus deoxygenated blood is

    increased leading to bluish

    discoloration of the skin (cyanosis)

    Polycythymia:

    *Definition: a disease state in which the proportion of blood volume that is occupied

    by red blood cells increases.

    *Types:

    1) Primary Polycythemia: Due to increased activity of hemocytoblastic cell of bone

    marrow.

    2) Secondary Polycythemia: Due to hypoxia.

    *Effects:

    We are sorry for any mistake in this lecture ,,,

    We want to thank ANMAR HADAD , and we wish to

    you all the success in medicine