The Blood

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The Blood
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The Blood

• Definition
• Blood is a connective tissue, not a body fluid,
  made of fluid (plasma) and cellular elements
  (RBC, WBC, and platelets)
• Its volume is 5-6 L in males and 4-5 L in
  females
• It is slightly alkaline, with a pH of 7.4
• Its color varies from bright to dark red
• It has a salty metallic taste

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The Blood

• Functions
• The blood is vehicular organ that reaches all the
  other tissues
• Transports oxygen and nutrients
• Removes CO2 and other by-products of cell
  activity
• Pivotal in maintaining homeostasis,
  growth and tissue repair
• Participates in the defense against
  infection
• Participates in hemostasis
• Participates in body heat distribution
  and regulation

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Marieb and Hoehn Human Anatomy Physiology
seventh edition Pearson Benjamin Cummings
5
The Blood

• Plasma
• Straw colored fluid made of water (90), other
  contents include
• Proteins make the bulk of the solutes
• Albumens (60), manufactured in the liver are
  the most abundant
• Globulins (36) are immune bodies
• Fibrinogen (4) for blood clotting
• Nutrients glucose, amino acids, lipids,
  cholesterol
• Electrolytes Na, K, Ca, Mg, H, Cl-,
  HCO3-, PO4--, SO4--
• Waste urea, creatinine, uric acid, bilirubin
• Gases O2 , CO2 , N2
• Protein bound hormones
• Plasma without clotting factors is called serum

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Peripheral blood smear
Marieb and Hoehn Human Anatomy Physiology
seventh edition Pearson Benjamin Cummings
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Electron micrograph of blood smear
Pathophysiology McCance Huether fifth edition
Elsevier Mosby
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The Blood

• RBC
• An RBC is a 7.5 micron disc shaped body with a
  central depression
• The cell is without a nucleus or mitochondria
• AN RBC contains hemoglobin and filamentous
  proteins attached to the cell wall to impart
  flexibility on it
• Antigens are embedded in the cell membrane, they
  decide the blood group
• The RBC cytoplasm provides energy to maintain
  intracellular homostasis
• This energy is generated mostly through
  anaerobic glycolysis
• RBCs function is gas exchange O2 to the tissues
  and CO2 to the lungs

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The Blood

• RBC
  
• Structure of Hemoglobin
• Each hemoglobin molecule is made up of four
  globin chains and four
• heme molecules
• Heme molecule is a porphyrin type pigment
  with a ferrous ion (Fe)
• Globin is a 287 amino acid protein made of
  two a, and two non a chains
• Adult hemoglobin A is (aa/ßß), fetal
  hemoglobin F is ( aa/??)
• An enzyme, 2,3 diphosphoglycerate (2,3 DPG)
  binds to hemoglobin
• molecule, it lowers its affinity to O2
• Binding of O2 to heme breaks some of the
  globin bonds exposing more
• heme molecules to bind with O2

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Structure of hemoglobin
Each heme molecule combines with one oxygen
atom
Marieb and Hoehn Human Anatomy Physiology
seventh edition Pearson Benjamin Cummings
11
Structure of hemoglobin and the oxygen
dissociation curve
Davidsons Principles and Practice of Medicine
eighth edition, Churchill Livingstone
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The Blood

• RBC
• Development of RBCs
• Hypoxia ? erythropoietin (kidney)? red marrow of
  long bones?
• erythroid stem cell? erythroblasts cell
  division? smaller cells loosing nucleus and
  gaining hemoglobin ? reticulocyte? mature RBC
• Reticulocytes contain remnants of cell
  organelles
• Their presence in excess in the peripheral
  blood (2) indicates
• excessive RBC destruction
• The normal number of RBCs is 4.3-5 million/mm3
  in the female and
• 5.1-5.8 million/mm3 in the male
• The normal values for Hgb are 13-15 gm/dl for
  females and
• 14-16 gm/dl in males
• Amino acids, lipids, carbohdrates, iron, vitamin
  B12 and folic acid are essntial for hemoglobin
  synthesis

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The Blood

• RBC
• Hemoglobin has a remarkable ability to bind with
  oxygen
• forming oxyhemoglobin
• It can also release the oxygen to the tissues
  becoming deoxyhemoglobin
• Hemoglobin combines with CO2 forming
  carbaminohemoglobin

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The Blood

• RBC
• Destruction
• Life span 120 days
• RBCs are phagocytosed by the reticulo-endothlial
  cells of the spleen
• Globulin is hydrolyzed to amino acids that
  are recycled
• Iron is removed from heme and reused to
  synthesize Hgb
• Heme remnant converted to bilirubin
• Bilirubin is conjugated with glucoronic
  acid, and secreted in bile
• In the intestine most is converted to
  stercobilin and excreted
• A small amount of stercobilin is
  absorbed by the kidney and
• secreted as urobilinogen

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The Blood

• RBC
• Disorders of RBCs
• Anemia is reduced RBC count
• Anemias can be caused by
• RBC loss or reduced production
• Hemorrhage, hemolysis, depressed bone
  marrow
• Reduced hemoglobin content of RBCs
• Iron, intrinsic factor, folic acid, or
  B12 deficiency
• Congenital hemoglobin defects
• Thalassemia, sickle cell anemia,
  spherocytosis

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The Blood

• RBC
• Disorders of RBCs
• Plolycythemia
• Bone marrow disorder causing an increased
  number of
• circulating RBCs and increased blood
  viscosity
• Aplastic anemia
• Results from bone marrow suppression or
  destruction (radiation,
• drugs, chemicals)
• All the blood elements are deficient

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Normal and sickle cell
RBC In sickle cell disease hemoglobin S replaces
the ß chain In thalassemias, the a or ß chains
can be absent or defective
Marieb and Hoehn Human Anatomy Physiology
seventh edition Pearson Benjamin Cummings
19
The Blood

• White Blood Cells (WBC)
• Function
• Lymphocytes are the effectors of the immune
  function
• WBCs main function is to fight bacterial
  infections
• WBCs are the only nucleated blood formed
  elements
• They exercise their functions in the tissues not
  the blood stream
• Selectines induce the WBC to adhere to
  capillary endothelium
• WBC migrate to the tissue spaces by diapeditic
  movement between
• endothelial cell, diapedesis is initiated
  by chemical attraction to
• the infection site initiated by damaged
  cells chemotaxis
• WBC destroy the bacterial cell wall by
  oxidation and digestion by
• proteins defensisns

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The Blood

• White Blood Cells (WBC)
• Types
• The total number of WBCs is 4000 to 10,000/mm3
• There two main types of WBCs granulucytes and
  agranulocytes
• Granulocytes, are of three types
• Neutrophils (polymorphs) 50-70,
  oxidize bacteria
• Eosinophils, 2-4 bilobed nuclei,
  attack parasites
• Basophils, 1 in peripheral blood,
  reside in the tissues,
• contain histamine, involved in
  hypersensitivity reaction

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The Blood

• White Blood Cells (WBC)
• Types
• Agranulocytes are of two types
• Lymphocytes, the smallest and second most
  abundant
• T cells (80) mediate cellular
  immunity, express CD1,2,3,4,5,7 8
• B cells mediate humoral immunity,
  express immunoglobulin light
• chains on the surface
• Monocytes, the largest, migrate to the
  tissues and become
• macrophages involved in cellular
  immunity, secrete IL1 , TNF, and
• CSF

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White blood cells, the granulcytes
Davidsons The Priciples and Practice of
Medicine, eigthteenth edition Churchill
Livingstone
23

Monocytes and lymphocytes
Davidsons The Priciples and Practice of
Medicine, eighteenth edition Churchill
Livingstone
24
The Blood

• WBC
• Development
• WBC production is Stimulated by two types of
  messengers
• Inerleukins IL-3 stimulates basophils (also
  RBCs and platelets)
• IL-5 stimulates eosinophils
• IL-3, IL-4 and IL-7 stimulate B
  lymphocytes
• IL-2, IL-4 and IL-7 stimulate T
  lymphocytes
• Colony stimulating factors (CSF)
• G-CSF stimulate neutrophils
  (granulocytes)
• GM-CSF stimulate eosinophils and
  monocytes
• WBC life span is 1 to 9 days

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Development of blood cells
Vanders Physiology eighth edition, Mc Graw Hill
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The Blood

• WBC
• Leukemias
• A single unspecialised WBC precursor cell
  clones itself uncontrollably
• The resulting leukemia is therefore
  monclonal
• The more undifferentiated cells produce acute
  (blastic) leukemias
• The more differentiated (cytic) cells
  produce chronic types
• A leukemia is called according to the
  producing cell
• Leukemias impair the bone marrow, and other
  blood cells functions
• Death is inevitable unless treated, it
  results from bleeding or sepsis

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The Blood

• Blood Coagulation
• Coagulation is a natural mechanism that acts to
  diminish blood loss from hemorrhage
• Coagulation (thrombosis) especially in the
  microcirculation is also a manifestation of
  inflammation and sepsis
• Coagulation occurs in three Stages
• Platelet plug
• The cascade leading to fibrin (clot)
  formation
• Clot retraction and repair (PDGF)

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The Blood

• Blood Coagulation
• The Platelets
• Structure and Function
• Platelets are discoid shaped bodies of 2-4 µm
  
• Derived from megacaryocytes arising from
  lineage committed stem cells
• They are fragments of cells, they have no
  nuclei
• They contain three types of granules in the
  cytoplasm
• Alpha granules contain fibrinogen and
  von Willebrand factor (vWF)
• Delta (dense) granules store adenosine
  diphosphate and serotonin
• Lysosomes, contain acid hydrolases

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The Blood

• Blood Coagulation
• The Platelets
• Platelets are activated by thrombin, collagen, or
  ADP, they discharge
• their content which leads to the
  formation of thrombaxane A2
• Platelets adhere to exposed collagen in the
  presence of
• von Willebrand factor (vWF)
• Their life span is 8-14 days, they are
  destroyed in the cells of the RE
• system

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The structure of a platelet
Davidsons The Priciples and Practice of
Medicine, eighteenth edition Churchill
Livingstone
31
Initial vasoconstriction and platelet plug
v
Vanders Physiology eighth edition Mc Graw Hill
32
Intrinsic and extrinsic coagulation pathways
Calcium ions are essential for the coagulation
cascade
Vanders Physiology eighth edition Mc Graw Hill
33
The role of the liver in blood coagulation
Vanders Physiology eighth edition Mc graw Hill
34
EM of a blood clot RBCs and fibrin
NIBSC?Science Photo Libraray Taken from Vander
Physiology eighth edition Mc Graw Hill

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Prostacyclin (PGI2 ) and nitric oxide inhibit
platelet aggregation
Vanders Physiology eighth edition Mc graw Hill
36
The Blood

• Anticoagulation
• Natural Anticoagulants
• Tissue factor pathway inhibitor (TFPI)
• Plasminogen - plasmin
• Heparin
• Antithrombin III
• Protein C
• Protein S
• Vitamin E quinone
• Natural anticoagulants also have anti
  inflammatory activity

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The Blood

• Anticoagulation
• Massive blood flow
• The (Intact) Endothelium
• Prevents platelet contact with collagen
• Displays heparin on its surface
• Secretes prostacyclin (PGAI2) and nitric oxide
• Activates protein C via attached
  thrombomodulin-thrombin complex
• Secretes tissue plasminogen activator

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The Blood

• Anticoagulation
• Heparin
• Is a natural anticoagulant found in the body
• Can be given by IV or subcutaneous routes for
  anticoagulation
• Can be easily neutralized (its action
  reversed) by protamine
• It has an antithrombin effect
• Inhibits platelet functions
• Its effect is measured by estimating the
  partial prothrombin time (PTT)

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The Blood

• Antigoagulation
• Aspirin (ASA)
• Inhibits cyclooygenase (COX) that catalyzes
  the formation of thrombaxane
• Mature platelets can not make new thrombaxane
  because their COX is
• blocked
• Endothelial cells can synthesize new COX,
  therefore they are not affected
• by ASA
• Thrombaxane is important for platelet
  aggregation
• Platelet function is assessed by the bleeding
  time
• New drugs that interfere with
  fibrinogen/platelet binding are now
• available

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The Blood

• Anticoagulation
• Vitamin K antagonists
• Warfarin, also known as coumadin
• Interfere with the liver synthesis of
  coagulation factors
• Effect measure by checking the protime (PT)
  now reported as
• international normalized ratio (INR)
• Vitamin E quinone is a potent anticoagulant

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Inactivation of Factors VIII V by thrombin
activated protein C
Vanders Physiology eighth edition Mc Graw Hill
42
Fibrinolysis, a mechanism for clot resorption
Vanders Physiology eighth edition Mc Graw Hill
43
The Blood

• Thrombolytics
• Plasminogen activates plasmin, a natural
  fibrinolytic agent
• Tissue Plasminogen Activator (t-PTA) activates
  plasminogen
• Plasmin dissolves an already formed clot
  (thrombolytic therapy)
• Streptokinase and Urokinase
• Thrombolytic action
• Streptokinase has side effects but less
  costly
• Urokinase has less side effects but more
  expensive
• New drugs that interfere with fibrinogen/platelet
  binding are now available

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The Blood

• Transfusion
• The following blood elements can be transfused to
  cover a deficiency
• in quantity or quality of one or more of the
  blood components
• Whole blood does not allow time for checking
  for the presence of
• infectious agents
• Packed RBCc for low Hb
• Platelets for thrompcytopenia and bleeding
• Plasma (fresh frozen) to replace deficient
  intrinsic factors
• Cryoprecipitate for hemophilia

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The Blood

• Transfusion
• Stored blood is acidified with citrates to
  prevent coagulation
• It looses its platelets
• Has more potassium, and accumulates ammonia
• More hemolysed RBC as the storage is prolonged
• Hemoglobin tends to hold more to O2 because of
  the reduction in
• 2,3 diphophoglyceric acid (2.3 DPG)
• The life span of RBCs stored at 4o C is about 28
  days

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The Blood

• Blood Types
• RBCs have surface antigens
• RBCs can be grouped according to the presence or
  absence of certain antigens
• There are many RBC antigens but only a A, B, AB
  and the Rh are of
• clinical significance
• Each one of the four types can be Rh positive or
  negative
• Donor blood is mixed with recipient serum to
  decide compatibility, donor cell clumping
  indicate incompatibility

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Major blood groups
A certain group posseses its antigen on the RBC
surface and antibodies against the others
Marieb and Hoehn Human Anatomy Physiology
seventh edition Pearson Benjamin Cummings
49
The Blood

• Transfusion
• Transfusion of incompatible RBCs results in their
  hemolysis in the donor
• This leads to blockage of the renal tubules,
  hypotension, fever, back pain, and may prove
  fatal
• This is treated by stopping the transfusion,
  hydration, and alkalinization of the urine
• Not every reaction to transfusion is due to
  infused RBC hemolysis,
• other less severe reactions can occur

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Identification of the RBC group
Marieb and Hoehn Human Anatomy Physiology
seventh edition Pearson Benjamin Cummings
51
The Blood

• Rh Factor
• There are no preformed Rh antibodies in Rh-
  individuals
• They develop after exposure to Rh factors
  (antigens)
• This explains the fact that an Rh fetus of an
  Rh- mother
• does not usually suffer
• But the Rh- mother can be sensitized to the Rh
  antigens during the first pregnancy, especially
  during delivery
• Subsequent fetuses can suffer from the mothers
  Rh antibodies passed
• to it and its blood hemolyzes
• This can be prevented by giving the mother serum
  that blocks the Rh
• factors antigenicity

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The Blood

• Rh Factor
• Eighty five percent of the population have Rh
  antigens (Rh)
• There are several Rh groups (factors, antigens)
• Three groups Rh, C, D, and E, are of clinical
  importance
• An Rh- mother may develop antibodies against her
  Rh fetus
• The Rh- mother antibodies can pass to the Rh
  fetus resulting in hemolysis of its RBCs, a
  condition know as erythroblastosis fetalis
• This sequence usually occurs after the first
  pregnancy