Blood

Chapter 14
  Blood: 
 A type of connective tissue with a liquid matrix
 Transports vital substances
 Maintains stability of interstitial fluid
 Distributes heat
Characteristics  Blood is about 8% of body weight; adult blood volume is about
4-5 liters in a female and 5-6 liters in a male

of Blood  Blood cells:

 Form mostly in red bone marrow, and are called “formed
elements”: 
 Red blood cells (RBC s)
 White blood cells (WBC s)
 Platelets (cell fragments)
Characteristics of
Blood
 Centrifuged Blood
Sample

 In a centrifuged blood sample:

 55% is plasma.
 45% is RBCs.
 WBCs and platelets are <1%.

 Percentage of RBCs is called the:

 Hematocrit (HCT) or packed cell
volume (PCV)
Blood Composition
 Hematopoiesis:
 Formation of blood cells
 Blood cells originate in red marrow from hemocytoblasts or
hematopoietic stem cells 
 Stem cells can then:
 Give rise to more stem cells.
 Give rise to more specialized or differentiated cells in
The Origin
response to hematopoietic growth factors:
 Lymphoid stem cells.
of Blood
 Myeloid stem cells.
 Lymphoid stem cells then give rise to lymphocytes
Cells
 Myeloid stem cells give rise to all other types of formed
elements: Red blood cells, other types of white blood cells,
and platelets
Blood Cells
 Characteristics of Red
Blood Cells

 Red blood cells (RBCs):  

 Also called erythrocytes.
 Biconcave disc shape.
 One-third hemoglobin:
 Oxyhemoglobin (with O2).
 Deoxyhemoglobin (without O2).

 Lack nuclei and mitochondria.

 Cannot divide.
 Can produce ATP through glycolysis.
  Red Blood Cell Count = number of RBCs in a cubic
millimeter (cm3) or microliter of blood
 Typical ranges include:

Red Blood Cell

RBC counts are useful in diagnosis of diseases and evaluation of
Counts their progress

Changes in RBC counts reflect changes in blood’s oxygen-

carrying capacity
 Red blood Cell Production
and Its Control

 Erythropoiesis:   
 RBC formation
 Occurs in red bone marrow.
 Low blood O2 causes kidneys and
liver to release EPO (erythropoietin),
which stimulates RBC production.
 A negative feedback mechanism.
 Hemocytoblast  --> erythroblast
--> reticulocytes --> erythrocytes
 Within a few days many new RBCs
appear in the blood
Substance Source Function Dietary Factors Affecting Red
Blood Cell Production
Vitamin B12 Absorbed from small
DNA synthesis
intestine

 Vitamin B12 and folic acid: Required for

Absorbed from small DNA synthesis; necessary for the
intestine; conserved
Hemoglobin growth and division of all cells.
Iron during red blood cell
synthesis
destruction and made
available for reuse  Iron: Required for hemoglobin
synthesis.

Absorbed from small

Folic acid DNA synthesis
intestine
 Types of Anemia

Type Cause Defect

Toxic chemicals,
Aplastic anemia Damaged bone marrow
radiation

Hemolytic anemia Toxic chemicals Red blood cells destroyed Anemia:

Iron-deficiency  Condition in which the O2-carrying capacity of the blood is
Dietary lack of iron Hemoglobin deficient
anemia reduced, due to deficiency of RBCs or hemoglobin  
Inability to absorb Excess of large, fragile
Pernicious anemia
vitamin B12 cells
Red blood cells
Sickle cell disease Defective gene
abnormally shaped

Hemoglobin deficient; red

Thalassemia Defective gene
blood cells short-lived
Table 14.3 Major Events in Red Blood Cell Destruction

1. Squeezing through the capillaries of active tissues damages red blood cells.

2. Macrophages in the spleen and liver phagocytize damaged red blood cells.

3. Hemoglobin from the red blood cells is decomposed into heme and globin.
Red Blood Cell
4. Heme is decomposed into iron and biliverdin.
Destruction
5. Iron is made available for reuse in the synthesis of new hemoglobin or is stored
in the liver as ferritin.

6. Some biliverdin is converted into bilirubin.

7. Biliverdin and bilirubin are secreted in bile as bile pigments.

8. The globin is broken down into amino acids metabolized by macrophages or

released into the plasma.
Life Cycle of a
Red Blood Cell 
RBC Destruction:
Hemoglobin
Breakdown
 Types of White Blood Cells

 White blood cells (Leukocytes, WBCs):

 Protect against disease.
 Leukocytes have limited life spans, so they must constantly be replaced.
 WBCs are produced in red bone marrow, under control of hormones: interleukins and colony-
stimulating factors.

 There are 5 types of WBCs, in 2 categories:

 •Granulocytes, which have granular cytoplasm, and short life span:
 Neutrophils.
 Eosinophils.
 Basophils.
 Agranulocytes, which do not have noticeable granules:
 Lymphocytes.
 Monocytes.
 Neutrophils

 Small, light purple granules in acid-

base stain.  
 Lobed nucleus; 2-5 sections.
 Also called PMNs, polymorphonuclear
leukocytes.
 First to arrive at infection site.
 Strong phagocytes.
 54% - 62% of leukocytes.
 Elevated in bacterial infections.
 Eosinophils

 Coarse granules; stain deep red in acid

stain.  
 Bi-lobed nucleus.
 Defend against parasitic worm
infestations.
 1% - 3% of leukocytes.
 Elevated in parasitic worm infestations
and allergic reactions.
 Basophils

 Large granules; stain deep blue in basic stain.

 Granules can obscure view of nucleus.
 Release histamine to stimulate inflammation.
 Release heparin to stop blood from clotting.
 Less than 1% of leukocytes.
 Similar to eosinophils in size and shape of
nuclei.
 Monocytes

 Largest of the WBCs.

 Spherical, kidney-shaped, oval or lobed nuclei.
 Agranulocytes.
 Leave bloodstream to become macrophages.
 3% - 9% of leukocytes.
 Live for weeks – months.
 Phagocytize bacteria, dead cells, debris.
 Lymphocytes

 Slightly larger than RBCs; smallest WBCs.

 Large spherical nucleus surrounded by thin rim of
cytoplasm.
 Agranulocytes.
 T cells and B cells are major types; both important
in immunity.
 T cells directly attack pathogens, tumor cells.
 B cells produce antibodies.
 25% - 33% of leukocytes.
 May live for years.
Functions of White Blood Cells

 Diapedesis: WBCs can squeeze between the cells of a capillary wall

and leave blood vessel; then migrate toward infection site.

 Cellular adhesion molecules: proteins that direct leukocytes to

injury sites.

 Phagocytosis: Engulfing and digestion of pathogens; neutrophils and

monocytes are most mobile and active phagocytes.

 Inflammatory response: Reaction that restricts spread of infection;

promoted by basophils, by secretion of heparin and histamine;
involves swelling and increased capillary permeability.

 Positive chemotaxis: Attraction of WBCs to an infection site, by

chemicals released by damaged cells.
Functions of White Blood Cells

Neutrophils respond to a bacterial invasion by

accumulating in the infection site, and destroying
the pathogens by phagocytosis
White Blood
Cell Counts
White Blood Cell
Illness
Population Change

Hairy cell leukemia, whooping

Elevated lymphocyte
cough, mononucleosis Abnormal White
Elevated eosinophils
Tapeworm infestation, hookworm
infestation, allergic reactions
Blood Cell
Typhoid fever, malaria,
Numbers
Elevated monocytes
tuberculosis

Elevated neutrophils Bacterial infections

Too few helper T cells

AIDS
(lymphocytes)
 Clinical Application: Leukemia

 Leukemia is a cancer of white blood cells.

 Classified as acute (symptoms appear suddenly & progresses rapidly), or chronic (begins
more slowly, may remain undetected for months or years).

 Lymphoid leukemia: Cancer of lymphocytes produced in lymph nodes.

 Myeloid leukemia: Cancer of granulocytes produced in red bone marrow.
 Symptoms of leukemia:
 Excess number of WBCs, fatigue, headache, nosebleeds, fever, respiratory infections,
bone pain, increased blood clotting time causing bruising and bleeding.

 Treatments include traditional cancer treatments (chemotherapy), drugs that target enzymes
specific to cancer cells, bone marrow or stem cell transplants, refining diagnosis.
Platelets
 Number
Component Description Function
Present
4,700,000–6,100,000 per
Red blood cell Biconcave disc without a nucleus, microliter, male Transports oxygen and carbon
(erythrocyte) about one-third hemoglobin 4,200,000 to 5,400,000 dioxide
per microliter, female
Destroys pathogenic
White blood cell 3,500 to 10,500 per
blank microorganisms and parasites and
(leukocyte) microliter
removes worn cells
About twice the size of red blood
Granulocytes cells; cytoplasmic granules are blank blank
present
Nucleus with two to five lobes;
cytoplasmic granules stain light 54%–62% of white blood
Cellular
Components of
    Neutrophil  Phagocytizes small particles
purple in combined acid and base cells present
stains
Nucleus bilobed; cytoplasmic 1%–3% of white blood Kills parasites and moderates
    Eosinophil

Blood
granules stain red in acid stain cells present allergic reactions
Nucleus lobed; cytoplasmic Less than 1% of white
    Basophil Releases heparin and histamine
granules stain blue in basic stain blood cells present

Agranulocytes Cytoplasmic granules are absent blank blank

Two to three times larger than a red

3%–9% of white blood
    Monocyte blood cell; nucleus shape varies Phagocytizes large particles
cells present
from spherical to lobed
Only slightly larger than a red
25%–33% of white blood
    Lymphocyte blood cell; its nucleus nearly fills Provides immunity
cells present
cell
150,000 to 350,000 per Helps control blood loss from
Platelet (thrombocyte) Cellular fragment
microliter broken vessels
 Clear, straw-colored.
 Liquid portion of blood.
 55% of blood volume.
 92% water. Plasma
 Contains organic and inorganic chemicals.
 Transports nutrients, gases, hormones, and vitamins.
 Helps regulate fluid and electrolyte balance and maintain pH.
 Plasma Proteins

Percentage of
Protein Origin Function
Total

Help maintain colloid osmotic

Albumins 60% Liver
pressure
 •Plasma proteins are the most abundant dissolved
Globulins 36%
substances (solutes) in plasma.
Transport lipids and fat-soluble
    Alpha globulins Liver
vitamins
 •Typically not used as energy source.
Transport lipids and fat-soluble
    Beta globulins Liver
vitamins

Lymphatic Constitute the antibodies of

    Gamma globulins
tissues immunity

Plays a key role in blood

Fibrinogen 4% Liver
coagulation
  Most important blood gases:
 Oxygen.
 Carbon dioxide.

 Plasma nutrients:
 Amino acids.
Gases and  Simple sugars.

Nutrients  Nucleotides.
 Lipids:
 Fats (triglycerides).
 Phospholipids.
 Cholesterol.
  Plasma contains ions called electrolytes, since they ionize in
water, and can conduct electricity.
 They are absorbed from the intestine or released as by-products
of cellular metabolism.
  Electrolytes found in blood plasma:
 Sodium.

Plasma 

Potassium.
Calcium.

Electrolytes 

Magnesium.
Chloride.
 Bicarbonate.
 Phosphate.
 Sulfate.

 Sodium and chloride are most abundant electrolytes.

  Hemostasis refers to the stoppage of bleeding.
 Actions that limit or prevent blood loss include:
 Blood vessel (vascular) spasm.

Hemostasis  Platelet plug formation.

 Blood coagulation.

 These mechanisms are most effective in small blood vessel

injuries.
  Stimulated by cutting or breaking a small blood vessel.
 Smooth muscle in blood vessel contracts rapidly.
 Slows blood loss very quickly, and ends of vessel may close
completely.
 Triggered by stimulation of the blood vessel wall, pain receptor

Vascular Spasm reflexes.

 Response lasts a few minutes, but effect continues for 30 minutes.
 This allows time for a platelet plug to form and blood to
coagulate.
 Serotonin released from platelets causes vasoconstriction which
further helps to reduce blood loss.
Platelet Plug Formation

§ Triggered by exposure of platelets to

collagen.
§ •Platelets adhere to rough surface to
form a plug.
 Blood Coagulation

 Most effective hemostatic mechanism, occurs within 5 to 15

minutes.

 Form blood clot in a series of reactions, in which each step

activates next one; this is called a cascade.

 Initiated by 2 different methods: Extrinsic or Intrinsic clotting

mechanism.

 Many chemicals used in coagulation are called clotting factors.

 Vitamin K necessary for functioning of some of the clotting

factors.

 Coagulation depends on balance between procoagulants and

anticoagulants.

 Major event is conversion of soluble fibrinogen to insoluble

threads of fibrin, which traps blood cells.
 Mechanism Stimulus Effect

Direct stimulus to Smooth muscle in

vessel walls or to vessel walls contracts
pain receptors; reflexly;
Vascular spasm
platelets release vasoconstriction helps
serotonin, a maintain prolonged
vasoconstrictor vascular spasm

Hemostatic Exposure of platelets Platelets adhere to

Mechanisms Platelet plug

formation
to rough surfaces or rough surfaces and to
to collagen of
connective tissue
each other, forming a
plug

Cellular damage and Blood clot forms as a

blood contact with result of a series of
Blood coagulation foreign surfaces reactions, terminating
activate factors that in the conversion of
favor coagulation fibrinogen into fibrin
  Triggered by damaged wall of blood vessel.
Extrinsic  Damaged tissues release tissue thromboplastin (factor III), which
is not found in blood.

Clotting  Cascade begins, involving sequential activation of several clotting

factors.

Mechanism  Thrombin converts fibrinogen into insoluble fibrin threads.

 Fibrin threads stick to damaged blood vessel surfaces, and trap
blood cells and platelets. This mass is a blood clot.
  Can start without tissue damage.
 Activated when blood comes in contact with foreign
surface, such as collagen, in connective tissue, instead of

Intrinsic endothelium of blood vessel wall.

Clotting  Triggered by Hageman factor XII (found inside blood).

 As in the extrinsic clotting mechanism, this begins
Mechanism sequential activation of several clotting factors.
 Results in the same way as extrinsic clotting mechanism,
with formation of a fibrin mesh and a blood clot.
 EXTRINSIC I N T R I NS I C
STEPS CLOTTING CLOTTING
M E C H AN I S M M E C H A NI S M

Damage to vessel or Blood contacts foreign

Trigger
tissue surface

Initiation Tissue thromboplastin Hageman factor

Blood
Series of reactions involving
several clotting factors and
calcium ions (Ca+2) lead to the
Prothrombin activator Prothrombin activator Coagulation
production of:

Prothrombin activator and calcium

Prothrombin to thrombin Prothrombin to thrombin
ions cause the conversion of:

Thrombin causes fragmentation,

Fibrinogen to fibrin Fibrinogen to fibrin
then joining of:
 Blood
Clotting
Mechanisms
  Cascade produces prothrombin activator

Positive  Prothrombin activator converts prothrombin to thrombin

Feedback  Thrombin stimulates increased activity of the intrinsic cascade

 This is an example of a positive feedback loop
Component Source Mechanism(s)
I (fibrogen) Synthesized in liver Extrinsic and intrinsic
Synthesized in liver,
II (prothrombin) Extrinsic and intrinsic
requires vitamin K
III (tissue thromboplastin) Damaged tissue Extrinsic
IV (calcium ions) Plasma electrolyte Extrinsic and intrinsic
Synthesized in liver,
V (proaccelerin) Extrinsic and intrinsic
released by platelets
VII (serum prothrombin Synthesized in liver,
conversion accelerator) requires vitamin K
Extrinsic
Clotting
Factors
Released by platelets and
VIII (antihemophilic factor) Intrinsic
endothelial cells
IX (plasma thromboplastin Synthesized in liver,
Intrinsic
component) requires vitamin K
Synthesized in liver,
X (Stuart-Prower factor) Extrinsic and intrinsic
requires vitamin K
XI (plasma thromboplastin
Synthesized in liver Intrinsic
antecedent)
XII (Hageman factor) Synthesized in liver Intrinsic
XIII (fibrin-stabilizing Synthesized in liver,
Extrinsic and intrinsic
factor) released by platelets
 Fate of Blood Clots

 After a blood clot forms, it retracts and pulls the edges of a broken blood vessel together while
squeezing serum from the clot.
 Serum = plasma minus fibrinogen and most clotting factors.
 Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged
blood vessel walls.
 Plasmin digests fibrin threads, and dissolves the blood clot.
 A thrombus is an abnormal blood clot that forms in a blood vessel.
 An embolus is a blood clot moving through the blood vessels.
Abnormal Blood Clot Formation

 Thrombosis: Blood clot in a vessel supplying a vital organ

(brain, heart)
 Infarction: Death of tissues which have blocked blood
vessels due to blood clot formation
 Embolism: Blood clot that travels, and then blocks a blood
vessel in an organ (such as pulmonary embolism in lungs)
 Atherosclerosis: Accumulation of fat in arterial linings can
sometimes cause abnormal clot formation; a common form
of thrombosis
  Deep Vein Thrombosis: Clot formation due to pooling of stagnant
blood, mainly in femoral or popliteal veins, or deep veins of
pelvis.

Clinical  Serious complication of DVT is a pulmonary embolism, in which

blood clot travels through circulation, and lodges in a pulmonary

Application: blood vessel, resulting in loss of function in affected portion of the

lung.

Deep Vein  Occurs with prolonged period of immobility, such as airplane

flight.

Thrombosis  Symptoms of DVT: deep muscle pain, cramping, redness,

swelling, and dilation of surface veins (phlebitis).
 Clot may break off hours or days after formation.
  The smooth lining of blood vessels discourages the
Prevention accumulation of platelets and clotting factors.

of
 As a clot forms, fibrin adsorbs (latches onto) thrombin and
prevents the clotting reaction from spreading.

Coagulation  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).
 Factors that Inhibit Blood Clot Formation

Factor Action
Prevents activation of intrinsic blood
Smooth lining of blood vessel
clotting mechanism
Inhibits adherence of platelets to blood
Prostacyclin
vessel wall
Fibrin threads Adsorbs thrombin
Antithrombin in plasma Interferes with the action of thrombin
Interferes with the formation of
Heparin from mast cells and basophils
prothrombin activator
 Blood Groups and Transfusions

 In 1910, identification of the ABO blood antigen gene explained the

observed blood type incompatibilities.
 Blood types are distinguished by antigens on the surfaces of red blood
cells, and these can be determined by the antigens or by the genes that
encode them.
 Antigen: Any molecule that evokes an immune response.
 If immune system finds a foreign antigen in the body, it
produces antibodies against the antigen.

 Antibodies: Proteins that react against a specific antigen.

 In an incompatible blood transfusion, donor red blood cells Blood
(RBCs) evoke an immune response in the recipient, and
antibodies in the recipient’s plasma agglutinate the donor
RBCs.
Antigens
 Agglutination: Clumping of RBCs, which occurs when an and
Antibodies
antibody (in recipient’s plasma) encounters its specific antigen
(on donor RBCs).
 There are 33 known antigens on RBC membranes, but only
a few can evoke a serious transfusion reaction.
 Only the antigens of the ABO and Rh groups evoke serious
transfusion reactions.
 ABO Blood Group

BLOOD  ABO Blood Group is based on the

ANTIGEN ANTIBODY
TYPE presence or absence of two major antigens
on red blood cell membranes: Antigen A
A A anti-B and Antigen B.
 Antigens A and B are carbohydrates.
B B anti-A
 Antibodies are associated with some
blood types; in general, a person produces
AB A and B Neither anti-A nor anti-B
antibodies against antigens that are not
present on his/her RBC membranes.
O Neither A nor B Both anti-A and anti-B  A person without A antigen has A
antibodies
 A person without B antigen has B
antibodies
Antigens and Antibodies of the 4 Blood Types
 Agglutination
When RBCs come in contact with antibodies against them, they will agglutinate (clump together).
 Compatible Blood Types
for Transfusions
If Preferred Blood
Type is Unavailable,
Blood Type of Preferred Blood
Permissible Blood  Type 0 = Universal Donor:
Recipient Type of Donor
Type of Donor (In an  Type O lacks the A and B antigens, so
Extreme Emergency) type O RBCs could be donated to
a person with any blood type. Often,
when given to a person with a different
blood type, only the RBCs are donated
A A O (since plasma contains antibodies).
B B O  Type AB = Universal Recipient: 
AB AB A, B, O  Type AB blood lacks both Anti-A and
Anti-B antibodies, so an individual with
O O No alternate types type AB can receive donor RBCs of any
type
  The Rh blood group was named for the rhesus monkey, in
which it was first studied.
 The group includes several Rh antigens or factors, but most
important one is antigen D.
 Rh positive: Presence of antigen D or other Rh antigens on
RBC membranes.
Rh Blood  Rh negative: Do not have the Rh antigens on RBC
Group membranes.
 Anti-Rh antibodies form only in Rh-negative individuals in
response to the presence of red blood cells with Rh antigens.
 The seriousness of the Rh blood group is evident in a fetus that
develops the condition erythroblastosis fetalis or hemolytic
disease of the newborn
Rh Incompatibility
Disorder
Chronic granulomatous disease
Erythrocytosis
Factor V Leiden
Hemophilia (several types)
Hereditary hemochromatosis
Porphyria variegata
Sickle cell disease
Von Willebrand disease
Some Inherited Disorders of Blood
Abnormality
Granulocytes cannot produce superoxide, which kills pathogenic bacteria
Reticulocytes have extra EPO receptors, enhancing stamina
Increases risk of abnormal clotting; elevates risk of deep vein thrombosis
Lack of specific clotting factor causes bleeding
Excess absorption of dietary iron into bloodstream deposits iron in various organs
Enzyme deficiency excretes porphyrin ring of hemoglobin into urine; metabolic blockage
causes sequence of varied symptoms
Abnormal hemoglobin crystallizes under low-oxygen conditions, sickling red blood cells,
which block circulation causing anemia, pain, and other symptoms
Lack of clotting factor (von Willebrand factor), which stabilizes factor VIII, causes bleeding;
less severe than hemophilia