Transcript I. Blood and Blood Cells

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?
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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
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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:
– RBC’s
– 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 blood’s 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 oxygencarrying 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 β-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 acidbase 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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3-7
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 (>50,000) 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
Gases
• oxygen
• carbon dioxide
Nutrients
• amino acids
• simple sugars
• nucleotides
• lipids
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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
Blood Vessel Spasm
• triggered by
pain receptors,
platelet release,
or serotonin
• smooth muscle
in vessel
contracts
Platelet Plug
Blood Coagulation
Formation
• triggered by
• triggered by
cellular damage
exposure of
and blood
platelets to
contact with
collagen
foreign surfaces
• platelets
• blood clot
adhere to
forms
rough surface
to form a plug
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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
Lymphoid Leukemia
• bone marrow produces
• lymphocytes are cancerous
too many immature
• symptoms similar to
granulocytes
myeloid leukemia
• leukemia cells crowd
out other blood cells
Treatments
• anemia
• drugs
• bleeding
• marrow and umbilical
• susceptible to
cord transplants
infections
• 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(9:22).
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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.
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