PowerPoint to accompany

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Chapter 14
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I. Blood and Blood Cells

• 1. Blood is three to four times more viscous
  than water.
• 2. Most blood cells form in red bone marrow.
• 3. Types of blood cells are red blood cells and
  white blood cells.
• 4. Cellular fragments of blood are platelets.
• 5. Formed elements of blood are the cells and
  platelets

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• What type of tissue is blood?
• Cells are suspended in what type of matrix?
• What are formed elements of blood?
• Answers
• connective tissue with a liquid extracellular
  matrix and containing suspended formed elements
  of white cells, erythrocytes, and platelets.

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Blood Volume

• varies with
• body size
• changes in fluid concentration
• changes in electrolyte concentration
• amount of adipose tissue
• about 8 of body weight
• about 5 liters

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B. Blood Volume and Composition

• 1. Blood volume varies with body size, changes
  in fluid and electrolyte concentrations, and the
  amount of adipose tissue.
• 2. Blood volume is about 8 of body weight.
• 3. An average-size adult has 5 liters of blood.

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B. Blood Volume and Composition

• 4. Hematocrit is the percentage of blood cells
  in a blood sample.
• 5. A blood sample is usually 45 red blood
  cells and 55 plasma.
• 6. Plasma is a mixture of water, amino acids,
  proteins, carbohydrates, lipids, vitamins,
  hormone, electrolytes, and cellular wastes.
• 7. Less than 1 of formed elements of blood are
  white blood cells and platelets and 99 are red
  blood cells.

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• What is the composition of the buffy coat?
• How can one separate blood components?
• Answers
• white blood cells and platelets
• centrifugation and settling

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Blood Composition
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• What is the hematocrit?
• What is a typical value for a hematocrit?
• What is another name for hematocrit?
• Answers
• of packed RBC volume in relation to overall
  total volume of all components.
• 45
• packed cell volume

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Figure 14.02
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• What percentage of blood is composed of plasma?
• What percentage of plasma is made of water?
• What gases are present in plasma?
• What proteins are found in plasma and what
  percentage of plasma do the constitute?

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Blood Plasma

• straw colored
• liquid portion of blood
• 55 of blood
• 92 water

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C. The Origin of Blood Cells

• 1. Blood cells originate in red bone marrow from
  hemocytoblasts or hemopoietic stem cells.
• 2. A stem cell can differentiate into any number
  of specialized cell types.
• 3. Colony-stimulating factors are growth factors
  that stimulate stem cells to produce certain cell
  types.
• 4. Thrombopoietin stimulates the production of
  megakaryocytes.

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Origin of Blood Cells
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• What is another name for an hemocytoblast?
• What marrow cell is the precursor for platelets?
• What is another name for platelets?
• Answers
• Hematopoietic stem cell
• Megakaryocytes
• Thrombocytes

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Figure 14.03aa
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Figure 14.03
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Characteristics of Red Blood Cells

• erythrocytes
• biconcave discs
• one-third hemoglobin
• oxyhemoglobin
• deoxyhemoglobin
• can readily squeeze through capillaries
• lack nuclei and mitochondria

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D. Characteristics of Red Blood Cells

• Red blood cells are also called erythrocytes.
• Red blood cells are biconcave in shape.
• The shape of red blood cells allow them to have
  an increased surface area for the transport of
  gases.
• Hemoglobin is an oxygen carrying protein in red
  blood cells.
• Each red blood cell is about one-third hemoglobin
  by volume.

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D. Characteristics of Red Blood Cells

• Oxyhemoblobin is hemoglobin combined with oxygen.
• Deoxyhemoglobin is hemoglobin that has released
  oxygen.
• Red blood cells extrude their nuclei as they
  mature.
• Because red blood cells lack mitochondria they
  must produce ATP through glycolysis.
• As red blood cells age, they become rigid and are
  more likely to be damaged and removed by enzymes
  in the liver and spleen.

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Figure 14.04a
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• Normal blood smear with
• RBCs
• Platelets (6 o'clock)
• Lymphocyte (center)

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Normal Blood Elements
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Cellular Blood Components
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Red Blood Cell Counts

• number of RBCs in a cubic millimeter of blood

• 4,600,000 6,200,000 in males

• 4,200,000 5,400,000 in adult females

• 4,500,000 5,100,000 in children

• reflects bloods oxygen carrying capacity

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Red Blood Cell Production

• low blood oxygen causes kidneys and liver to
  release erythropoietin which stimulates RBC
  production

• vitamin B12, folic acid and iron necessary

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F. Red Blood Cell Production and Its Control

• Erythropoiesis is red blood cell production.
• Initially, red blood cell formation occurs in the
  yolk sac, liver and spleen.
• After an infant is born, red blood cells are
  produced almost exclusively in the red bone
  marrow.
• Hemocytoblasts in red bone marrow give rise to
  erythroblasts that give rise to erythrocytes.

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F. Red Blood Cell Production and Its Control

• Reticulocytes are immature red blood cells that
  still contain endoplasmic reticulum.
• The average life span of a red blood cell is 120
  days.
• Erythropoietin controls red blood cell production
  and is released primarily from the kidneys.
• When the availability of oxygen decreases,
  erythropoietin is released and red blood cell
  production increases.

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Life Cycle of Red Blood Cell

• circulate for about 120 days

• macrophages in spleen and liver destroy worn out
  RBCs

• hemoglobin is broken down into heme and globin

• iron from heme returns to red bone marrow

• bilirubin and biliverdin excreted in bile

Figure 14.06
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Figure 14.08
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Dietary Factors Affecting Red Blood Cell
Production

• Two vitamins needed for red blood cell production
  are vitamin B12 and folic acid.
• Intrinsic factor is needed for the absorption of
  vitamin B12.
• Iron is required for hemoglobin production.
• Anemia is a reduction in the oxygen-carrying
  capacity of the blood.

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Dietary Factors Affecting Red Blood Cell
Production
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Types of Anemia
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Anemia
Normal RBCs
RBCs of person with hypochromic anemia
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• What is the amino acid substitution that results
  in sickle cell anemia?
• What hemoglobin subunit is affected?

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Sickle Cell

• Single DNA base change causes addition of a
  single different amino acid in hemoglobin
• Hgb crystallizes in low oxygen
• Sickle cells cause blockages in small vessels
• Causes excruciating joint pain and organ damage

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Sickle Cell

• Consequences of hemolysis include chronic anemia,
  jaundice, predisposition to aplastic crisis,
  cholelithiasis, and delayed growth and sexual
  maturation.
• Vascular occlusion and tissue ischemia can result
  in acute and chronic injury to virtually every
  organ of the body, most significantly the spleen,
  brain, lungs, and kidneys.

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Sickle Cell

• Though in early childhood the spleen may be
  enlarged with sickle cell anemia, continual
  stasis and trapping of abnormal RBC's leads to
  infarctions that eventually reduce the size of
  the spleen tremendously by adolescence. This is
  sometimes called "autosplenectomy". Seen here is
  the small remnant of spleen in a patient with
  sickle cell anemia.

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Sickle Cell

• Molecular Genetic Pathogenesis
• Hemoglobin S results from the substitution of
  valine for glutamic acid in the second nucleotide
  of the sixth codon of the ß-globin chain.

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Sickle Cell

• Diagnosis/testing.  
• The term sickle cell disease encompasses a group
  of symptomatic disorders associated with
  mutations in the HBB gene and defined by the
  presence of hemoglobin S (Hb S).

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Sickle Cell

• Newborn screening.
• Because of the high morbidity and mortality of
  sickle cell disease in undiagnosed toddlers, all
  50 states, the District of Columbia, Puerto Rico,
  and the Virgin Islands currently provide
  universal screening for sickle cell disease. The
  vast majority of new cases are diagnosed at
  birth.

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Sickle Cell
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Destruction of Red Blood Cells
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Destruction of Red Blood Cells

• Damaged red blood cells rupture as they pass
  through the spleen or liver.
• In the liver and spleen, macrophages destroy worn
  out red blood cells.
• Hemoglobin molecules are broken down into globin
  and heme groups.
• Heme decomposes into iron and biliverdin.

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Destruction of Red Blood Cells

• Ferritin is an iron-protein complex that stores
  iron in the liver.
• Biliverdin is converted to bilirubin.
• Bilirubin and biliverdin are excreted in bile.
• The polypeptide globin chains breakdown into
  amino acids.

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White Blood Cells

• leukocytes
• protect against disease
• interleukins and colony-stimulating factors
  stimulate development

• granulocytes
• neutrophils
• eosinophils
• basophils

• agranulocytes
• lymphocytes
• monocytes

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Neutrophils

• light purple granules in acid-base stain
• lobed nucleus
• other names
• segs
• polymorphonuclear leukocyte
• bands (young neutrophils)
• first to arrive at infections
• phagocytic
• 50 - 70 of leukocytes
• elevated in bacterial infections

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Eosinophils

• deep red granules in acid stain
• bilobed nucleus
• moderate allergic reactions
• defend against parasitic worm infestations
• 2 - 4 of leukocytes
• elevated in parasitic worm infestations and
  allergic reactions

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Basophils

• deep blue granules in basic stain
• release histamine
• release heparin
• less than 1 of leukocytes
• similar to eosinophils in size and shape of
  nuclei

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Monocytes

• largest blood cell
• spherical, kidney-shaped, oval or lobed nuclei
• leave bloodstream to become macrophages
• 2 - 8 of leukocytes
• phagocytize bacteria, dead cells, and other
  debris

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Lymphocytes

• slightly larger than RBC
• large spherical nucleus surrounded by thin rim
  of cytoplasm
• T cells and B cells
• important in immunity
• B cells produce antibodies
• 20 - 40 of leukocytes

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Figure 14.09
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Figure 14.10
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Figure 14.11
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Figure 14.12
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Figure 14.13
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Diapadesis

• leukocytes squeeze between the cells of a
  capillary wall and enter the tissue space outside
  the blood vessel

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Cell Adhesion Molecules

• guide cells on the move

• selectin allows white blood cells to anchor

• integrin guides white blood cells through
  capillary walls

• important for growth of embryonic tissue

• important for growth of nerve cells

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Positive Chemotaxis

• movement of leukocytes toward the damaged tissue
  region because of the chemicals that were
  released by damaged cells

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White Blood Cell Counts

• procedure used to count number of WBCs per cubic
  millimeter
• of blood
• 5,000 10,000 per cubic millimeter of blood

• leukopenia
• low WBC count (below 5,000)
• typhoid fever, flu, measles, mumps, chicken pox,
  AIDS
• leukocytosis
• high WBC count (above 10,000)
• acute infections, vigorous exercise, great loss
  of body fluids

• differential WBC count
• lists percentages of types of leukocytes
• may change in particular diseases

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White Blood Cell Counts
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Atypical Lymphocytes
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The RBCs in the background appear normal. The important finding here is the presence of many PMN's. An elevated WBC count with mainly neutrophils suggests inflammation or infection. A very high WBC count (gt50,000) that is not a leukemia is known as a "leukemoid reaction". This reaction can be distinguished from malignant WBC's by the presence of large amounts of leukocyte alkaline phosphatase (LAP) in the normal neutrophils.
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Blood Platelets

• thrombocytes
• cell fragments of megakaryocytes
• 150,000 350,000 (approximate) per cubic
  millimeter
• of blood
• helps control blood loss from broken vessels

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Blood Plasma

• straw colored
• liquid portion of blood
• 55 of blood
• 92 water

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Plasma Proteins
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Gases and Nutrients

• Nutrients
• amino acids
• simple sugars
• nucleotides
• lipids

• Gases
• oxygen
• carbon dioxide

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Nonprotein Nitrogenous Substances

• molecules containing nitrogen but are not
  proteins
• urea product of protein catabolism about 50
  of NPN substances
• uric acid product of nucleic acid catabolism
• amino acids product of protein catabolism
• creatine stores phosphates
• creatinine product of creatine metabolism
• BUN blood urea nitrogen indicate health of
  kidney

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Plasma Electrolytes

• absorbed from the intestine or released as
  by-products of cellular metabolism

• sodium
• potassium
• calcium
• magnesium
• chloride
• bicarbonate
• phosphate
• sulfate
• sodium and chloride are most abundant

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Hemostasis

• stoppage of bleeding

• Platelet Plug Formation
• triggered by exposure of platelets to collagen
• platelets adhere to rough surface to form a plug

• Blood Vessel Spasm
• triggered by pain receptors, platelet release,
  or serotonin
• smooth muscle in vessel contracts

• Blood Coagulation
• triggered by cellular damage and blood contact
  with foreign surfaces
• blood clot forms

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Platelet Plug Formation
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Blood Coagulation

• Coagulation
• hemostatic mechanism
• causes the formation of a blot clot via a series
  of
• reactions which activates the next in a cascade
• occurs extrinsically or intrinsically

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Blood Coagulation

• Extrinsic Clotting Mechanism
• chemical outside of blood triggers blood
  coagulation
• triggered by thromboplastin (not found in blood)
• triggered when blood contacts damaged tissue

• Intrinsic Clotting Mechanism
• chemical inside blood triggers blood coagulation
• triggered by Hageman factor (found inside blood)
• triggered when blood contacts a foreign surface

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Blood Coagulation
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Table 14.09
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Blood Coagulation
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Figure 14.19b
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Fate of Blood Clots

• After forming, a blood clot retracts and pulls
  the edges of a broken vessel together while
  squeezing the fluid serum from
• the clot

• Platelet-derived growth factor stimulates smooth
  muscle cells and fibroblasts to repair damaged
  blood vessel walls

• Plasmin digests blood clots

• thrombus abnormal blood clot
• embolus blood clot moving through blood

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Prevention of Coagulation

• The smooth lining of blood vessels discourages
  the accumulation of platelets and clotting factors

• As a clot forms, fibrin adsorbs thrombin and
  prevents the clotting reaction from spreading

• Antithrombin inactivates additional thrombin by
  binding to it and blocking its action on
  fibrinogen

• Some cells, such as basophils and mast cells
  secrete heparin (an anticoagulant)

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Prevention of Coagulation
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Figure 14.20
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Antigens and Antibodies
Agglutination clumping of red blood cells in
response to a reaction between an antibody and an
antigen Antigens a chemical that stimulates
cells to produce antibodies Antibodies a
protein that reacts against a specific antigen
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Antigens and Antibodies
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Agglutination
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Agglutination
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Figure 14.22c
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Figure 14.22d
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ABO Blood Group

• Based on the presence or absence of two major
  antigens on red blood cell membranes
• antigen A
• antigen B

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Questions

• What is the main concern when blood is
  transfused?
• Why is type AB a universal recipient?
• Why is type O a universal donor?

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ABO Blood Group
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Blood Types for Transfusion
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Questions

• What is the Rh blood group?
• What are ways that Rh incompatibility
• arise?

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Rh Blood Group
Rh positive presence of antigen D and/or other
Rh antigens on the red blood cell membranes Rh
negative lack of these antigens
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Question

• What is erythroblastosis fetalis?
• How is it prevented?

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Rh Blood Group
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Clinical Application
Leukemia

• Myeloid Leukemia
• bone marrow produces too many immature
  granulocytes
• leukemia cells crowd out other blood cells
• anemia
• bleeding
• susceptible to infections

• Lymphoid Leukemia
• lymphocytes are cancerous
• symptoms similar to myeloid leukemia

• Treatments
• drugs
• marrow and umbilical
• cord transplants
• chemotherapy regimens

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In contrast to aplastic anemia, leukemia results in a highly cellular marrow. The marrow between the pink bone trabeculae seen here is nearly 100 cellular, and it consists of leukemic cells of acute lymphocytic leukemia (ALL) that have virtually replaced or suppressed normal hematopoiesis. Thus, though the marrow is quite cellular, there can be peripheral cytopenias. This explains the complications of infection (lack of normal leukocytes), hemorrhage (lack of platelets), and anemia (lack of red blood cells) that often appear with leukemia.
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Figure 14.aa
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Figure 14.ab
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Figure 14.a
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There are numerous granulocytic forms seen here, including immature myeloid cells and bands. This condition is one of the myeloproliferative states and is known as chronic myelogenous leukemia (CML) that is most prevalent in middle-aged adults. A useful test to help distinguish this disease is the leukocyte alkaline phosphatase (LAP) score, which should be low with CML and high with a leukemoid reaction.
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Here is another view of a peripheral blood smear in a patient with CML. Often, the numbers of basophils and eosinophils, as well as bands and more immature myeloid cells (metamyelocytes and myelocytes) are increased. Unlike AML, there are not many blasts with CML.
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Myeloid cells of CML are also characterized by the Philadelphia chromosome (Ph1) on karyotyping. This is a translocation of a portion of the q arm of chromosome 22 to the q arm of chromosome 9, designated t(922).
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Here are very large, immature myeloblasts with many nucleoli. A distincitve feature of these blasts is a linear red "Auer rod" composed of crystallized granules. These findings are typical for acute myelogenous leukemia (AML) that is most prevalent in young adults.
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Leukemias typically fill up the marrow with abnormal cells, displacing normal hematopoiesis. The marrow here is essentially 100 cellular, but composed almost exclusively of leukemic cells. Normal hematopoiesis is reduced via replacement (a "myelophthisic" process) or by suppressed stem cell division. Thus, leukemic patients are prone to anemia, thrombocytopenia, and granulocytopenia and all of the complications that ensue, particularly complications of bleeding and infection.
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At high power, the bone marrow of a patient with acute myelogenous leukemia is seen here. There is one lone megakaryocyte at the right center.
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The WBC's seen here are lymphocytes, but they are blasts--very immature cells with larger nuclei that contain nucleoli. Such lymphocytes are indicative of acute lymphocytic leukemia (ALL). ALL is more common in children than adults. Many cases of ALL in children respond well to treatment, and many are curable.
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These mature lymphocytes are increased markedly in number. They are indicative of chronic lymphocytic leukemia, a disease most often seen in older adults. This disease responds poorly to treatment, but it is indolent.