circulatory system by xiaoyounan


        The Circulatory System: Blood

n   Blood Functions
    and properties
n   Blood cell
n   Erythrocytes (RBC)
n   Leukocytes (WBC)
n   Hemostasis
n   Blood types
Normal Blood Values

n   Hemoglobin concentration
    • Women 12-16 g/dL
    • Men 13.5-17.5 gm/dL
n   Hematocrit
    • Women 37-47%
    • Men 40-54%
n   Mean corpuscular volume
    • 87- 95 fl/RBC
n   The study of blood
    • (Hemo = blood, -ology = study)
n   Blood is as unique as your fingerprints
n   Most cells cannot move around to get
    oxygen and nutrients and get rid of
    waste, the blood system does this for
n   INTO the BLOOD- Oxygen from the
    lungs, nutrients from the small
n   OUT OF the BLOOD- Waste goes out
    the kidneys, skin and large intestine

n   The heart pumps 5-6 liters of blood per
    minute through the circulatory system.
n   Blood is an aqueous mixture
    consisting of plasma and cells.
       Functions of Blood

n   Distribution - nutrients, wastes, hormones,
    gases, etc.

n   Self-sealing – hemostasis

n   Disease/ infection fighting
                Blood = connective tissue

extracellular                specialized cells:
matrix:                      (= Formed elements)


color ?                      Platelets
volume ?
Plasma Composition

                    Transports organic and
                    inorganic molecules,
                    formed elements, and heat

                n   Water            92%
                n   Plasma proteins 7%
                n   Other solutes      1%
          Plasma Proteins

n   Albumin (60%) Major contributor to osmotic concentration
    of plasma. Transport of lipids and steroid hormones

n   Globulins (35%) Transport ions, hormones, lipids;
    immune function

n   Fibrinogen (4%) Essential component of clotting system
    (conversion to insoluble fibrin)

n   Regulatory proteins (< 1%) ????
       Other Solutes

n   Electrolytes: Normal extracellular fluid
    ion composition (????)

n   Organic nutrients: glucose, FA, AA

n   Organic wastes: urea, bilirubin
Formed Elements
            Red and White
              Blood Cells

            n   Platelets
            n   WBCs           .1%

            n   RBCs
Formed Elements
     cont.        Why white blood cells???
         RBCs = Erythrocytes

Measured by hematocrit

Most abundant blood cell: 1000 RBCs/1 WBC

Contain hemoglobin, carry O2

Very regular shape - biconcave discs

Anucleate: Lifespan ~ 120 days replacement
  rate ~ 3 mio RBCs / sec
  WBCs = Leukocytes
Quantity and type determined by     Granulocytes and
  differential WBC count

Circulating WBCs are only a small
   fraction of total WBCs.
 Neutrophil (= PMN)

Up to ~ 70% (~ 2/3) of circulating WBCs
Cytoplasm packed with pale granules containing lysosomal


~ 2% - 4% of circulating WBCs
Granules stain with eosin
Increased in allergies and parasitic infections
n   < 1% of circulating WBCs
n   Granules stain with basic dyes and contain histamine
n   Discharge of histamine promotes inflammation at site of injury (Similar
    to mast cells)
n   ~ 2% - 8% of circulating WBCs
n   Large kidney shaped nucleus
n   In tissue called Macrophage

n   ~ 20% - 30% of circulating WBCs
n   Relatively small (slightly larger than RBCs)
n   Large round nucleus
n   B, T, NK
  Platelets = Thrombocytes

Cell fragments of Megakaryocytes
   (~ 4,000 thrombocytes per Megakaryocyte)
 ~ 160 m
Lifespan ~ 12 days
involved in blood                        clotting
Abnormal Blood Cell Counts

Leukopenia < 2,500/ L (normal 6000 – 9000)
Leukocytosis > 30,000/ L

Thrombocytopenia: < 80,000/ L (normal ~ 350,000)
Thrombocytosis:     > 1,000,000/ L
Hemopoiesis = Blood Cell Formation

 Hemocytoblasts: One type of stem cell for all blood cells

                                    . . . then differentiation
                                    into 4 types of
                                    progenitor stem cells:
                                        Myeloblast      Fig 20.8

                       In red bone marrow

n   A straw-colored liquid consisting of
    approximately 90% water and 10%
n   The proteins are albumin, globulins,
    and fibrinogen.
         Functions and Properties of

n   Function: Helps cells get nutrition, gets rid of
n   Two types of fluid: Blood and Interstitial
    • Blood is the transported
    • Interstitial fluid is the diffuser
Two Functions of Blood

n   1. Transport- oxygen, nutrients, waste
n   2. Protection- clotting, immunity =
    white blood cells (WBC), interferon,
The main function of blood
1.    Respiration (transport of O2 a CO´2)
2.    Nutrition (transport of ingested nutrients)
3.    Transportation of waste products
4.    Transport of heat (for heating and cooling)
5.    Acid-base balance
6.    Water balance
7.    Thermoregulation
8.    Immunity
9.    Transport of hormones (signals), vitamins and trace
10.   Hemocoagulation (hemostasis)
Physical Characteristic of Blood

n   Alkaline: 7.4 pH avg.
n   8 % of body weight (if you were a $100
    bill, about $8 of you would be blood)
n   Blood volume: 1.2 gallon female, 1.5
    gallon male
n   Temperature of the blood is a little
    higher than body temperature, WHY?
Components of Blood

n   If Blood is spun down (centrifuged), we
    see two parts:
    • 1. Plasma- liquid
       – If this is allowed to clot what remains is called
    • 2. Cells- bottom of tube
       – Cells of the blood are mostly red blood cells
         (RBCs). The rest, only 1%, is basically
         platelets and white blood cells (WBCs)
Main components

 n   Whole blood (8% of body weight) = blood
     elements + blood plasma

 n   erythrocytes 4.2 – 6.0 x1012/l
 n   leukocytes 3 – 11 x109/l
 n   thrombocytes 170 – 360 x109/l

 n   serum x plasma

 n   Hematokrit 36% - 49%
Centrifuging Blood

 n   Centrifuging blood forces cells to separate from plasma
 n   Hematocrit is the % of total volume of cells
 n   Normal crit = females 42 avg., males 47 avg.
                   Components of Whole Blood

                                       (55% of whole blood)

                                       Buffy coat:
                                       leukocyctes and
                                       (<1% of whole
1   Withdraw blood
    and place in tube   2 Centrifuge
                                       (45% of whole

                                                              Figure 17.1
Hematocrit Tells Us…

n   Hematocrit of 40 means that 40 % of
    the blood is __ __ __s
    • Does a doctor do a hematocrit to determine
      the amount of WBCs or platelets? YES NO
    • Then what is in the buffy coat? ________ (A
      vampire slayer?)

n   Abnormal:
    • Low crit =Anemia, decreased ________
    • High crit = Polycythemia
        Plasma Proteins

n   3 major categories of plasma proteins
    • Albumins are most abundant plasma protein
    • Globulins (antibodies) provide immune system
       – alpha, beta and gamma globulins
    • Fibrinogen creates fibrin threads that causes blood
      to clot
Plasma proteins

n   Oncotic pressure (colloidal-osmotic) (3
    kPa), edema
n   Synthesis in liver
n   glycoprotein (except albumin)
n   Proteins of acute phase (CRP)
n   70-80 g/l
n   Blood volume
1. Albumin

n   32-45 g/l, 69 kDa, 60 % of all plasma
    proteins, 80 % of oncotic pressure
n   12 g/day produced in liver (25 % of
n   Liver diseases – decrease of A:G ratio
n   585 AK, ellipsoidal shape (15 x 3.8 nm)
n   albuminuria
n   transport: FFAcids, Ca, bilirubin,
    steroid hormones, Cu, penicillin,
2. Haptoglobin
n   Glycoprotein binding free Hb (10 % Hb of
    destroyed erythrocytes, the rest breaks down
    into globin, hem and iron), 0.4- 1.8 g/l of Hp,
    the same amount of Hb, 90 kDa
n   free Hb is filtrated in kidney and may affect
    tubules (transfusion)
n   Hp-Hb complex is not filtrated: iron sparing
    and tubules protecting effects
n   Decreases during hemolytic anemia (half-
    times of Hp-Hb and Hp), increases during
    inflammation (PAF)
3. Iron coupled proteins

n   transferin (2-4 g/l), feritin (plasma level
    corresponds to the body reserve),
n   hemochromatosis
4. Ceruloplazmin

n   2-globulin, 160 kDa, 0.3 g/l
n   Transfer of 90 % of copper (6 atoms bind to
    one molecule), the rest is transported bound
    to albumin, easy release = probably more
n   Connected to the Wilson disease
    (hepatolenticular degeneration, AR, storage of
    copper in the brain, cornea, kidney and liver,
    high intestinal adsorption and low liver
    excretion of copper; Hepatitis, anemia,
    neurological signs, Kayser-Fleischer ring; )
5. 1-antitrypsin

n   The main component of 1 fraction
n   Inhibits the trypsin, elastase and other
n   deficiency (mutation) results in
    accumulation of the 1-AT in
    hepatocytes, hepatitis and cirrhosis
    (unknown mechanism), transplantation
      6. Immunoglobulins

      n   Produced by plasma cells (B-
      n   antibodies, the defense proteins

            IgG    IgA     IgM      IgD     IgE
g/l        9-15   1.5-4   0.6-1.7   0-1.4

kDa         150    160     900      180     190
         Formation of Blood Cells

n   Hemopoiesis- Blood making
    • Lymphoid hemopoiesis occurs in widely distributed
      lymphoid tissues (thymus, tonsils, lymph nodes,
      spleen & peyers patches in intestines)
    • red bone marrow produces RBCs, WBCs and platelets
      – 1.) Stem cells
      – 2.) Committed cells
      – 3.) Precursor Cells
      – 4.) Final blood cells
Formed Elements of Blood

n   Never Let Monkeys Eat Bananas- quantities of
Hypoxia: An important concept

n   Cellular oxygen deficiency is hypoxia
    (hypo= under, ox= oxygen)
    • Ischemia is a from of hypoxia due to
      obstruction of blood flow (as by the
      narrowing of arteries by spasm or disease)
n   This can cause cell death (necrosis)
n   Occurs in many situations:
    • High altitude
    • Anemia
    • Iron or B12 deficiency resulting in anemia
    • Circulatory problems
Erythrocyte Homeostasis
n   Classic negative feedback control
    • drop in RBC count causes hypoxemia to
    • stimulation of bone marrow
    • RBC count  in 3-4 days
n   Stimulus for erythropoiesis
    • Hypoxia is a stimulus for blood production
      such as:
       – low levels of atmospheric O2 (high altitude)
       – increase in exercise
       – Circulatory problems
       – Anemia from Iron or B12 deficiency
Erythropoiesis: Making RBCs
         RBC creation

        In bone marrow

        Nucleus Ejected

         Mature RBC
        Regulation of the erythropoesis

 tissue oxygenation (blood volume, anemia, hemoglobin,
 perfusion, lungs)
n stimulation
   • erythropoietin
                              – glucocorticoids
   • somatotropin
                              – estrogens
   • thyroxin
   • rennin-angiotensin
   • testosterone
     Lab Test for RBC creation
•Reticulocyte count (“Tic”) measures the rate of
erythropoiesis and so can give an indication of RBC
•Normal= avg. 1 %--- because about 1% of RBCs are
replaced in a day therefore about 1% of the blood is
   •Low tic count = red bone marrow not working.
   Cause = nutritional deficiency or leukemia
   •High tic count = usually good sign, response to iron
Erythrocytes (RBCs)

n   Biconcave discs, anucleate, essentially
    no organelles
n   Filled with hemoglobin (Hb), a protein
    that functions in gas transport
n   Contain the plasma membrane protein
    spectrin and other proteins that:
    • Give erythrocytes their flexibility
    • Allow them to change shape as necessary
Erythrocytes (RBCs)

n   Erythrocytes are an example of the
    complementarity of structure and
n   Structural characteristics contribute to
    its gas transport function
    • Biconcave shape that has a huge surface
      area relative to volume
    • Discounting water content, erythrocytes
      are more than 97% hemoglobin
    • ATP is generated anaerobically, so the
      erythrocytes do not consume the oxygen
      they transport
    Erythrocyte Function
n   Erythrocytes are dedicated to
    respiratory gas transport
n   Hemoglobin reversibly binds with
    oxygen and most oxygen in the blood
    is bound to hemoglobin
n   Hemoglobin is composed of the protein
    globin, made up of two alpha and two
    beta chains, each bound to a heme
n   Each heme group bears an atom of
    iron, which can bind to one oxygen
n   Each hemoglobin molecule can
    transport four molecules of oxygen
Production of Erythrocytes

n   Hematopoiesis – blood cell formation
n   Hematopoiesis occurs in the red bone
    marrow of the:
    • Axial skeleton and girdles
    • Epiphyses of the humerus and femur
n   Hemocytoblasts give rise to all formed
Production of Erythrocytes:

                              Figure 17.5
of Red

         Figure 17.7
Red Blood Cells (RBCs)

              n   RBCs are called erythrocytes
                  (red, cells)
              n   Oxygen-carrying cells
              n   Contains oxygen-carrying
                  protein called hemoglobin
              n   Anatomy- 7.5 microns,
                  biconcave disc- can get into
                  small places
                  • large surface area helps
                    diffusion of gases
              n   No nucleus or organelles so
                  ample space for oxygen
              n   Gets energy anaerobically
                  • So it doesn’t need the
                    oxygen that it’s carrying
Erythrocytes on a Needle
          Erythrocytes and Hemoglobin

n   RBC count & hemoglobin concentration indicate
    the amount of oxygen the blood can carry
    • hemoglobin concentration of whole blood
       – men avg. 15; women avg. 14
    • RBC count
       – men 5.5 million avg.; women 5 million avg.
       Erythrocyte Death & Disposal

n   RBCs live for 120 days
    • membrane fragility -- lysis in narrow channels in
      the spleen through a process called ____________
n   Macrophages in spleen
    • remove iron from heme
    • convert heme to bilirubin (yellow pigment)
n   Why can’t RBCs repair themselves?
n   Bilirubin is converted to urobilogen in the
    intestine by bacteria giving fecal matter it’s
    brown color
Structure of Hemoglobin

                          Figure 17.4

n   Oxyhemoglobin – hemoglobin bound
    to oxygen
    • Oxygen loading takes place in the lungs
n   Deoxyhemoglobin – hemoglobin after
    oxygen diffuses into tissues (reduced
n   Carbaminohemoglobin – hemoglobin
    bound to carbon dioxide
    • Carbon dioxide loading takes place in the
     Types of globin chains

        Hb A    2b2 The main adult Hb
        Hb B    2s2 adult, 2.5% Hb
        Hb F    2g2 fetal, higher affinity to O2
        Gower   t 2 e2   embryonic
        Gower 2e2 embryonic
physiological: oxyhemoglobin, carbaminohemoglobin
pathological: carboxyhemoglobin, methemoglobin
Hemoglobin saturation curve

          Right handed shift = decrease of
             the affinity = increase of the
             oxygen release:
          1. decrease of pH (Bohr effect)
          2. Increase of pCO2
          3. Increase of temperature
          4. Increase of 2,3-DPG (product of
             anaerobic glykolysis (for NaK ATPase),
             binds to the Hb, not to the oxyHb)
Fetal hemoglobin

n   37 AA out of 146 differ from the b chain
    (adult one)
n   Binds low 2,3-DPG, shifted to the left
    compared with the adult one at the
    same level of pO2
n   Hemoglobin saturation curve shifted to
    the left

DEGRADATION of the hemoglobin
Heme – biliverdin – bilirubin (bile)

            n   In the muscle tissue
            n   sat. curve shifted to
                the left
                • Oxygen is released
                  only under very low
                  levels of pO2 (long-
                  term contraction)
                • Binds oxygen from
                  the blood
Metabolism of the Iron

n   food: Fe3+ x more absorbable Fe2+
    • Gastric juice (acidity, gastroferrin) and
      vitamin C reduces Fe, (following partial
      gastric resection sideropenic anemia
n   Absorbed in the upper part of small
    intestine (duodenum)
n   Fe2+ plasma level 10-35 mol/l
Metabolism of the Iron

 n   apoferritin (mucosa), transferrin (2 Fe3+;
     plasma; b1-globulin), ferritin (4500 Fe3+;
     spleen, liver, bone marrow; plasma
     ferritin, rapidly available iron reserve),
     hemosiderin (aggregated ferittin, is less
     readily mobilized)
 n   Iron requirement: 0.2 mmol/day
     (adsorption 6% in male, 12 % in female
     = 0.02 mmol/d losses per day; high req.
     (0.5 mmol/day) during menstruation,
     second half of pregnancy and after
The iron distribution


            Nutritional Needs for
n   B12 & folic acid (for rapid cell division) and vitamin
    C & copper synthesizing RBCs
n   Iron is key nutritional requirement for
    • lost daily through urine, feces, and bleeding
    • low absorption rate requires consumption of 5-20 mg/day
       – Maintain supplement for six months to replace liver storage
    • dietary iron in 2 forms: ferric (Fe+3) & ferrous (Fe+2)
    • ferrous is the form of iron used by the body (For US two)
       – stomach acid converts Fe+3 to absorbable Fe+2
Iron Blood Tests

  • Transferrin blood test determines how much
    iron is bound to the protein that carries
    iron in the blood (Trans-port)
  • Serum ferritin test shows the level of iron in
    the liver (FerritIN the liver)
      CBC Blood Test

n   Complete Blood Count (CBC) is a composite
    of blood tests that measures certain
    components of the blood.
n   RBCs, WBCs and platelets are counted
n   ______= the total blood volume of RBCs is
n   A “diff” (differential of WBCs) is included
n   Hemoglobin content is included- which
    measures the amount of the oxygen carrying
    protein found in the RBCs
Leukocytes (WBCs)

n   Leukocytes, the only blood
    components that are complete cells:
    • Are less numerous than RBCs
    • Make up 1% of the total blood volume
    • Move through tissue spaces
n   Leukocytosis – WBC count over 11,000
    per cubic millimeter
    • Normal response to bacterial or viral
        Leukocyte Production

n   Some lymphocytes leave bone marrow
    • go to thymus to complete their development (T cells)
n   Circulating WBCs do not stay in bloodstream
    • granulocytes leave in 8 hours
    • monocytes leave and transform into macrophages
    • WBCs provide long-term immunity lasting decades

n   leukocytes 3 – 11 x109/l = 3000 –
n   heterogennic population, only one
    common parameter – the defense
    function: defense against tumors,
    bacterial, viral and parasitical
    White Blood Cells (WBCs)
    WBC are also called Leukocytes (leuko= white, cyte=
    old cell)
    -Have nucleus but no hemoglobin

n    GRANULAR                n   AGRANULAR
n    Neutrophils             n   Lymphocytes
n    Eosinophils             n   Monocytes
n    Basophiles
     Granular Leukocyte (WBCs)
n   Granulocytes- when stained these show
    granules under the microscope
    • basophils – non-abundant, dark violet granules
       – large U- to S-shaped nucleus hidden by granules
    • eosinophils - pink-orange granules & bilobed
      nucleus (2-4%)
    • neutrophils - multilobed nucleus (60-70%)
       – fine reddish to violet granules in cytoplasm
       – Older neutrophils are called polymorphonuclear
         (PMN) leukocytes or “POLYS”
    • BEN
n   Neutrophils ( in bacterial infections)
    • phagocytosis of bacteria
    • releases antimicrobial chemicals
n   Eosinophils ( in parasitic infections
    or allergies)
    • phagocytosis of antigen-antibody complexes,
      allergens & inflammatory chemicals
    • release enzymes destroy parasites such as
n   Basophils ( in chicken pox, sinusitis,
    • secrete histamine (vasodilator)
    • secrete heparin (anticoagulant)
Agranular Leukocyte (WBCs)

n   These cells do contain granules but do
    not stain and are small
n   Monocytes- the cops of the body
n   The blood is a transport system (cop
    car) for monocytes as they fight
    infection in tissues
    • They go into tissue and become
      macrophages (macro= big, phage= eater)
n   Lymphocytes- cytoplasm stains and
    forms a blue rim around the cell
    • B cells, T cells and Killer cells
n   Lymphocytes ( in diverse infections
    immune responses)
    • destroy cancer & foreign cells & virally
      infected cells
    • coordinate actions of other immune cells
    • secrete antibodies & provide immune
n   Monocytes ( in viral infections &
    • differentiate into macrophages
    • phagocytize pathogens and debris

n   Major types are B cells, T cells, and
    natural killer cells which are major
    warriors in the immune response
n   B cells- from Bone marrow
    • Good at destroying Bacteria
n   T cells- Formed in bone marrow but
    matures in the Thymus gland
    • Good at attacking virus, fungi, cancer cells
      and Transplanted organs
n   Killer cells- kill microbes and tumor
      Types of white blood cells

poly-       neutrophils   3000-6000/l   50-70%
nuclear     eosinophils   150-300/l     1-4%
granulocyte basophils     0-100/ l      0-0.5%
lymphocytes               1500-4000/l   20-40%

monocytes                 300-600/l     2-8%
the function
   n   neutrophils: second line of defense; shield against
       invading bacteria, chemotaxis (diapedesis, amoeboid
       motion), phagocytosis
   n   eosinophils: mucous immunity, against non-
       phagocytable agents (mostly parasites)
   n   basophiles: immediate allergic reaction (anaphylactic
       shock), release of histamin, heparin…
   n   monocytes: 72 h circulating, then migration into
       tissues (RES), phagocytosis, first line of defense
   n   lymphocytes:
       • T-lymphocytes: cell immunity (helper, suppressor, cytotoxic,
         memory cells)
       • B-lymphocytes: humoral immune defense (plasma cells,
         memory cells)

n   Granulocytes – neutrophils,
    eosinophils, and basophils
    • Contain cytoplasmic granules that stain
      specifically (acidic, basic, or both) with
      Wright’s stain
    • Are larger and usually shorter-lived than
    • Have lobed nuclei
    • Are all phagocytic cells

n   Neutrophils have two types of granules
    • Take up both acidic and basic dyes
    • Contain peroxidases, hydrolytic enzymes,
      and defensins (antibiotic-like proteins)
n   Neutrophils are our body’s bacteria

n   Eosinophils account for 1–4% of WBCs
    • Have red-staining, bilobed nuclei
      connected via a broad band of nuclear
    • Have red to crimson (acidophilic) large,
      coarse, lysosome-like granules
    • Lead the body’s counterattack against
      parasitic worms
    • Lessen the severity of allergies by
      phagocytizing immune complexes

n   Account for 0.5% of WBCs and:
    • Have U- or S-shaped nuclei with two or
      three conspicuous constrictions
    • Are functionally similar to mast cells
    • Have large, purplish-black (basophilic)
      granules that contain histamine
       – Histamine – inflammatory chemical that acts as
         a vasodilator and attracts other WBCs
         (antihistamines counter this effect)

n   Agranulocytes – lymphocytes and
    • Lack visible cytoplasmic granules
    • Are similar structurally, but are functionally
      distinct and unrelated cell types
    • Have spherical (lymphocytes) or kidney-
      shaped (monocytes) nuclei

n   Account for 25% or more of WBCs and:
    • Have large, dark-purple, circular nuclei with
      a thin rim of blue cytoplasm
    • Are found mostly enmeshed in lymphoid
      tissue (some circulate in the blood)
n   There are two types of lymphocytes: T
    cells and B cells
    • T cells function in the immune response
    • B cells give rise to plasma cells, which
      produce antibodies

n   Monocytes account for 4–8% of
    • They are the largest leukocytes
    • They have abundant pale-blue cytoplasms
    • They have purple-staining, U- or kidney-
      shaped nuclei
    • They leave the circulation, enter tissue, and
      differentiate into macrophages

n   Macrophages:
    • Are highly mobile and actively phagocytic
    • Activate lymphocytes to mount an immune
Summary of Formed Elements

                             Table 17.2
Summary of Formed Elements

                             Table 17.2
           Formation of Leukocytes
n   All leukocytes originate from hemocytoblasts
n   Hemocytoblasts differentiate into myeloid stem cells
    and lymphoid stem cells
n   Myeloid stem cells become myeloblasts or
n   Lymphoid stem cells become lymphoblasts
n   Myeloblasts develop into eosinophils, neutrophils,
    and basophils
n   Monoblasts develop into monocytes
n   Lymphoblasts develop into lymphocytes
Formation of Leukocytes

                          Figure 17.11
WBC Pathology

n   Leukocytosis- increased WBCs
    • usually normal
    • Due to stresses such as microbes and
      strenuous exercise
n   Leukopenia- decreased WBCs
    • Abnormal
    • due to shock or drug reactions or disease
Increased and Decreased WBCs

n   INCREASED              n   DECREASED
n   Neutrophils-           n   Neutrophils-
    bacteria                   radiation, drugs,
                               nutrition deficiency
n   Lymphocytes- virus
                           n   Lymphocytes-
n   Monocytes-virus,           chronic illness
    fungus                 n   Monocytes-bone
n   Eosinophils-allergy,       marrow depression
    parasites              n   Eosinophils-drugs,
n   Basophils- allergy,        stress
    cancer                 n   Basophils-
                               pregnancy, stress
WBC pathology- Leukemia

n   Leukemia = cancer of hemopoietic
    • Uncontrolled WBC production
    • Subject to opportunistic infection, anemia
n   Acute Leukemia- = immature WBC
n   Chronic Leukemia- = too many WBCs
    • Remission (disappearing) and
      exacerbation (occurrence) common
    Normal and Leukemia Blood

n   Normal blood ratio = 700 RBCs to 1
        The Action of WBCs
n   WBCs leave the bloodstream by emigration
n   Phagocytosis- the process of the WBC eating an
    invader, a bacteria
n   Chemotaxis- the process of attracting
    phagocytes, caused by toxins that are
    produced by microbes destroying tissue
n   Lysozymes- enzymes that the phagocytes use to
    destroy bacteria
n   A Differential WBC count (Diff) is counting of the
    different WBC, determining the percentage of
    each type of WBC helps in the diagnosis
 n   Platelets are fragments of
     megakaryocytes with a blue-staining
     outer region and a purple granular
 n   The granules contain serotonin, Ca2+,
     enzymes, ADP, and platelet-derived
     growth factor (PDGF)
 n   Platelets function in the clotting
     mechanism by forming a temporary
     plug that helps seal breaks in blood
Platelet Production

n   Cells called megakaryocyte create
n   Cytoplasm of the cell splits off creating
    cell fragments that enter the
    bloodstream as platelets (live for 10
    • some stored in spleen & released as
n   Platelets are important for _________
          Genesis of       Platelets
n   The stem cell for platelets is the hemocytoblast
n   The sequential developmental pathway is
    hemocytoblast, megakaryoblast,
    promegakaryocyte, megakaryocyte, and platelets

                                             Figure 16.12

n   A series of reactions designed for
    stoppage of bleeding
n   During hemostasis, three phases
    occur in rapid sequence
    • Vascular spasms – immediate
      vasoconstriction in response to injury
    • Platelet plug formation
    • Coagulation (blood clotting)
        Platelet Plug Formation
n   Platelets do not stick to each other or to the
    endothelial lining of blood vessels
n   Upon damage to a blood vessel, platelets:
    • Are stimulated by thromboxane A2
    • Stick to exposed collagen fibers and form a platelet
    • Release serotonin and ADP, which attract still more
n   The platelet plug is limited to the immediate
    area of injury by PGI2

                                Scanning electromicrograph of
                                activated platelets

Scanning electromicrograph of
   n   A set of
       reactions in
       which blood
       from a liquid
       to a gel
   n   Coagulation
       intrinsic and
       pathways        Figure 16.13a
n   The final thee steps
    of this series of
    reactions are:
    • Prothrombin activator
      is formed
    • Prothrombin is
      converted into
    • Thrombin catalyzes
      the joining of
      fibrinogen into a fibrin

                                 Figure 16.13a
Reactions of

               Figure 16.13b
                Of Thrombosis and Embolism
n   Unwanted coagulation
    • Thrombosis = the formation of a clot of blood within a
      blood vessel
       – Thrombosis can create a thrombus
    • Thrombus = a clot of blood formed within a blood vessel
      and remaining attached to its place of origin
       – most likely to occur in leg veins of inactive people
       – the thrombus may break off causing an embolus
    • An embolus is an abnormal particle circulating in the
       – An embolus could travel from veins to lungs producing
         pulmonary embolism
       – death from hypoxia may occur
n   Necrosis = Tissue death
n   Infarct = an area of necrosis in a tissue
    or organ resulting from obstruction of
    the local circulation
n   Infarction is the process of forming an
    • may occur if an embolus or thrombus
      blocks blood supply to an organ (MI or
    • 650,000 Americans die annually of
Blood has the ability to clot together.                  This is
                good and bad, depending.

                                  n   BAD
        n   GOOD                  n   Thrombosis- blood
        n   Hemostatis- the           clotting in vessels
                                      forming BLOOD CLOTS
            process of stopping
                                  n   Embolism- a blood clot,
            the bleeding              or air bubble or fat, that
            process                   blocks a vessel causing
                                  n   Hemorrhage- blood loss.
                                      Can be from drugs like
                                      anticoagulants, or
                                      vessel tear
        Anticoagulant Drugs

n   Warfarin or Coumadin (rat poison) may be given
    to people who have a tendency to produce
    blood clots, like in atrial fibrillation
n   Their blood must be monitored for possible
n   These drugs are antagonists to vitamin K
n   Streptokinase- produced from streptococcal
    bacteria is a thrombolytic agent, it dissolves
    blood clots both good and bad. Used in stroke
          Hemostasis - The Control of

n   Platelet plug is formed by pseudopods that adhere to the
    vessels and contract drawing the vessel together
n   Fibrin, a sticky protein, comes from the plasma to trap
    blood cells
         Blood Types

n   The surface of RBCs contain genetically determined
    antigens (antibody generator) these determine the blood
n   Major blood types are: ABO and Rh
n   ABO blood group are based on people that have blood
    antigens A or B
n   If you have A antigen on your RBCs you are type A, if
    you have B antigens you are type B, and type AB has
    both antigens but if you don’t have any A or B antigens
    you are type O.
n   Remember: This applies to incoming blood
    ABO Blood typing:
    4 combinations possible

n   A surface antigen = blood type A
n   B surface antigen = blood type B
n   both surface antigens = type AB
n   neither surface antigen = type O

n   Rh surface antigen = + blood type
n   no Rh antigen = negative blood type
   . . . 2 - 8 months after birth:

Anti-A and anti-B antibodies can be formed in
plasma !

                                  normally NO
                                  anti Rh present
          Transfusion Reaction
Transfusion of incompatible blood can be fatal!

Universal Donor vs.
    Universal Recipient
Only for emergencies - must be
given slowly !
Blood Type Diet Theory

n   Type O is said to be the Original blood
    type, no antigens. These were the
    hunters. Diet is meat based. Native
    Americans are 79% type Os.
n   Type A is the Agrarian blood type.
    These are the farmers. Diet is
ABO Blood Typing
                   n   Agglutination is
                       the term for
                       blood clumping
                   n   For example:
                       type A has
                       agglutination on
                       the left which
                       tells us this
                       blood reacted
                       with anti-A
                   n   Type AB has
                       agglutination to
                       both ____ and
Blood Swapping
n   Type AB- universal ABceptor, person
    can be infused with any type of blood
n   Type O- universal dOnor, can give their
    blood to anyone
n   Caveat: Remember that blood contains
    other antigens and antibodies than
    ABO, so specific typing should always
    be done to avoid Agglutination
n   Agglutination is massive clumping
    which is distinct from normal clotting
    (like from a cut)
Mismatched Transfusion
            The Rh Group
n   Rh or D agglutinogens discovered in Rhesus monkey
    • If you have the Rh antigen you are Rh+
    • If you don’t have the Rh antigen you are Rh-
n   Anti-D agglutinins are not normally present in blood
    • formed only in individuals exposed to Rh+ blood
        – Rh- pregnant woman carrying an Rh+ fetus
        – no problems result with the first pregnancy
        – hemolytic disease of the newborn (erythroblastosis fetalis) occurs if
          mother has formed antibodies & is pregnant with 2nd Rh+ child
    • RhoGAM is given to pregnant woman to prevent antibody
      formation and prevent any future problems

n   Relate disease: Chocolate should be avoided in ____
    peanut butter cup syndrome
             Hemolytic Disease of Newborn

n   Mother’s antibodies attack fetal blood causing toxic brain
    syndrome from excessive bilirubin in blood from hemolysis
    • treatment is phototherapy to degrade bilirubin or complete exchange
      transfusion to replace all the infant’s blood
Lymphatic System

n   A separate vessel system.
n   The two main functions are to transport
    excess fluid from the interstitial spaces
    to the circulatory system and to protect
    the body against infectious organisms.
Components of the Lymph

n   Lymph Fluid: pale yellow; moves from
    the plasma through the capillary walls
    and becomes interstitial fluid.
n   Lymph Nodes: scattered through the
    body and contain dense patches of
    lymphocytes and macrophages.
n   Lymph Organs: the spleen and the
  The Lymphatic
Palpable superficial lymph nodes

    Posterior auricular
    Superficial cervial
    Deep cervical
               Lymph System

n   Lymphatic capillaries
n   Lymphatic ducts
n   Lymph Nodes
n   System carries fluids from the interstitial
    spaces to the blood
n   Proteins, fat from GI, and hormones return to
n   Returns excess interstitial fluid to blood
Lymphatic Circulation
Lymphocyte development:
  Overview of
Peripheral Blood
              BLOOD SMEAR - very lucky view
                    3 PMNs/Neutrophils 2 Lymphocytes
                    1 Monocyte 1 Eosinophil 1 Basophil
        Mon               Clumped platelets Many RBCs

                                       The presence of the
                                       rare basophil makes
              Eos                      this an unlikely view.
                                       Beware of mistaking
      Lym                              the clumped
                                       chromatin of a small
                                       lymphocyte’s nucleus
                                       for the purple
                                       cytoplasmic granules
      Lym                  Bas         of the basophil

                    Peripheral Blood
                    n   RBC size should
                        be about the size
                        of a lymphocyte
                    n   The area of central
                        pallor in a RBC
                        should be about
                        1/3 of total RBC

40x magnification
Normal Peripheral
n   RBC size should be
    about the size of a
    lymphocyte nucleus
n   The area of central
    pallor in a RBC should
    be about 1/3 of total
    RBC diameter
           Peripheral Blood

       n   The area of central
           pallor in a RBC should
           be about 1/3 of total
           RBC diameter

Disorders of Red Cell Size

                     n   Anisocytosis refers
                         to red cells which
                         vary widely in size.
                     n   The RDW
                         measures the range
                         of red cell sizes.
Disorders of Red Cell Size

                     n   Microcytosis refers to
                         red cells that are small.
                     n   You can use the
                         lymphocyte nucleus as a
                         visual reference, or you
                         can use the MCV
                     n   Associated with
                         • Iron deficiency
                         • Thalassemias
                         • Sideroblastic anemia
Macrocytic RBCs
                  Disorders of Red
                  Cell Size
                  n   Macrocytosis refers to large red
                  n   Compare the macrocytic cells to
                      normal red cells shown below.
                  n   Use the MCV.
                  n   Associated with
                      • Elevated reticulocyte count
                      • B12/folate deficiency
Normal RBCs
                      • Liver disease
                      • Thyroid disease
                      • Chemotherapy
                      • Anti-retrovirals (AZT)
Disorders of Red Cell Color

                   n   Hypochromasia refers
                       to red cells that have too
                       little hemoglobin.
                   n   The area of central
                       pallor is more than 1/3
                       the total red cell
                   n   This is measured by the
Disorders of Red Cell Color

                     n   Polychromasia
                         refers to red cells
                         that have more of a
                         bluish tinge.
                     n   In general, these
                         blue cells (see
                         arrows) are larger
                         and are probably
Disorders of Red Cell Shapes

                    n   Poikilocytosis refers
                        to red cells that vary
                        widely in shape.
                    n   Remember that
                        anisocytosis refers
                        to red cells that vary
                        widely in size.
Disorders of Red Cell Shapes

                 n   Target cells look like bulls-
                 n   Associated with
                     • Liver disease
                     • Thalassemias
                     • Hemoglobin C
                     • After splenectomy
Disorders of Red Cell Shapes

                  n   Spherocytes have a loss
                      of central pallor.
                  n   Can be seen in
                      • Hereditary spherocytosis
                      • Autoimmune hemolysis
                  n   If due to autoimmune
                      hemolysis, the cells are
                      smaller (i.e.
Disorders of Red Cell Shapes

                    n   Schistocytes are red
                        cell fragments with
                        sharp edges.
                    n   They are a hallmark
                        of Microangiopathic
                        Hemolytic Anemia
Disorders of Red Cell Shapes

                    n   Sickle Cells are seen
                        in sickle cell anemia.
                    n   Notice that this slide
                        has target cells as
                        well as a sickled
echinocytes         Disorders of Red Cell

                       n   Echinocytes, or burr
                           cells, have small,
                           regular projections.
                           Seen in renal disease
                       n   Acanthocytes, or spur
                           cells, have larger,
                           irregular projections,
                           and are seen in liver

Disorders of Red Cell Shapes

                    n   Teardrop cells are
                        seen in
                        processes, or
                        diseases of marrow

n   Howell-Jolly bodies are peripheral, small,
    round, purple inclusions within red cells that
    represent nuclear remnants.
n   They are seen after splenectomy, or in cases
    of splenic hypofunction.
                                       Disorders of Red
                                       Cell Distribution

n   Rouleaux are linear arrangements of red cells typically
    described as “piles of coins on a plate”
n   They are typically seen in disorders with increased levels of
    immunoglobulin, such as Multiple Myeloma or
    Waldenstrom’s macroglobulinemia.
n   Severe hypo-albuminemia can also lead to rouleaux
                         Disorders of Red Cell

n   Red cell agglutination occurs when the red cells
    are coated with IgM. IgM is large enough to bridge
    two red cells and cause agglutination.
n   Unlike rouleaux, the red cell clumps are not orderly
    and linear.
Iron Deficiency Anemia

                         , microcytic
                         numbers of
                         platelets can
                         be seen.
Iron Deficiency Anemia

n   Red cells are
n   Hypersegmented
    neutrophils can be
Autoimmune Hemolytic
   Anemia (AIHA)

n   Polychromasia
    (black arrows)
n   Microspherocytes
    (green arrows)
Microangiopathic Hemolytic Anemia
Sickle Cell Anemia
Sickle Cell Anemia
                    White Blood Cells

n   Polymorphonuclear neutrophils, AKA polys, segs, PMNs
    have fine pink granules and segmented nuclei
White Blood Cells
n   Band neutrophils, AKA bands are immature
n   There is no segmentation of the nucleus.
             White Blood Cells

n   Lymphocytes have a thin rim of blue cytoplasm
    and a dark purple nucleus, which should be the
    same size as red cells.
             White Blood Cells

n   Monocytes are large cells with slate blue
    cytoplasm and folded nuclei.
n   Vacuoles can be present.
                       White Blood Cells

n   Eosinophils have chunky red granules and are typically
n   Basophils have deep purple granules that overlie the

      basophil         eosinophil
Acute Leukemia
           n   Blasts are very
               large cells with
               large nuclei with
               fine, open
               chromatin. They
               may have nucleoli.
           n   The only way to
               between AML and
               ALL on the smear
               is if there are Auer
               Rods (black
               arrows) present.

      1-3. Small
      4. PMN
      5. Smudge cell

1.   Basophil     5. Myeloblast
2.   Eosinophil   6. Myelocyte
3.   Myelocyte    7. Myeloblast
4.   PMN          8. Metamyelocyte

      1.   Promyelocyte
      2.   Myelocyte
      3.   Band
      4.   Myelocyte
      5.   Early band or

 1.   Band
 2.   Myeloblast
 3.   Band
 4.   Myelocyte
 5.   Myelocyte
 6.   Metamyelocyte

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