Indri N. Rahayu, dr, MKes.

Bagian Ilmu Faal FK UHT

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Overview: Composition of Blood
 A liquid connective tissue
 A mixture
 the formed elements - living blood cells & platelets
 the plasma – the fluid matrix
 Denser and more viscous than water
 due to dissolved ions & organic molecules, especially plasma
proteins, and to the blood cells
 composition and volume regulated by CNS & hormones
 Temp - 38° C
 pH - 7.4 (critical to be between 7.35 and 7.45)
 Volumes differ between sexes, conditional on many factors
 Females - average 4-5 L
 Males - average 5-6 L

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Functions of Blood
 Transport and Distribution
 delivery of O2, nutrients, and hormones
 removal of CO2 and metabolic wastes
 Regulation of Internal Homeostasis
 body temperature
 pH
 fluid volume
 composition of the interstitial fluid/lymph
 Protection
 necessary for inflammation and repair
 prevents blood loss by hemostasis (coagulation)
 prevents infection

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 Transport O2 and CO2
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 The movement of body fluid

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Components of Blood - Plasma
 Proteins important
for osmotic balance
 albumin (60%)
○ transports lipids
○ steroid hormones
 fibrinogen (4%) -
blood clotting
 globulins (35%) –
many different
proteins with a wide
variety of functions
 globulin classes α,
β, and γ
 1% other regulatory
proteins
Components of Blood - Plasma
 Other solutes
 Waste products -
carried to various
organs for removal
 Nutrients – glucose
and other sugars,
amino acids, lipids,
vitamins and
minerals
 Electrolytes (ions)
 Regulatory
substances
○ enzymes
○ hormones
 Gases - O2, CO2, N2
Components of Blood - Formed
Elements

 Formed elements
 >99% red blood cells
 <1% white blood cells
and thrombocytes
(platelets)
RBC Physiology

 O2 combines with Hgb in lungs

 O2 not very soluble in H2O
 O2 needs a molecular transporter to carry it
 Hemoglobin
 4 globin (protein) chains - 2 α chains & 2 β chains
 4 non-protein heme pigments (lipid)
 each heme pigment has iron ion (Fe²+) that carries 1 O2
 each RBC can carry about 1 billion O2 molecules
 RBC's carry ~25% of the CO2 bound to Hgb - forms
carbaminohemoglobin
Carbaminohemoglobin
 With low oxygen (peripheral capillaries):
 hemoglobin releases oxygen which makes
plasma CO2 elevated
 Alpha and beta chains binds carbon dioxide
and carries it to lungs
 Carbaminohemoglobin is formed
 RBC then absorb O2 and releases CO2

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RBC Life Span
 Life span
 only 100-120 days
 cannot repair damage due to loss of nucleus, ribosomes

 Old RBC’s destroyed in the spleen, liver and the bone marrow
 Macrophages eat old RBC's
 Breakdown products are recycled
 Different pathways exist for each part of the Hgb molecule
○ globin chains - AA's used for other protein synthesis
○ heme
 iron portion - Fe2+ recycled
 non-iron lipid portion – converted to bilirubin - waste
- released into blood, secreted by the liver into bile
- bile enters intestine, is converted to urobilinogen by bacteria
- contributes to urine & feces color
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Recycling RBCs

Figure 19–4
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Recycling RBCs
 1% of circulating RBCs wear out per
day:
 about 3 million RBCs per second
 Macrophages of liver, spleen, and bone
marrow:
 monitor RBCs
 engulf RBCs before membranes rupture
(hemolyze)

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Hemoglobin Recycling
 Phagocytes break hemoglobin
into components:
 globular proteins to amino acids
 heme to biliverdin
 iron

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 Iron Recycling
 To transport proteins (transferrin)
 To storage proteins (feritin and hemosiderin)

Matter11/8/2019
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Form and 2012-2013 2003
Iron Metabolism: Key to Hemoglobin O2 Transport

11/8/2019 Figure 16-8: Iron 2012-2013

Blok Hematology metabolism 17
Breakdown of Biliverdin
 Biliverdin (green) is converted to
bilirubin (yellow)
 Bilirubin is:
 excreted by liver (bile)
 jaundice is caused by bilirubin build
up
 converted by intestinal bacteria to
urobilins and stercobilins

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Erythropoiesis

 hypoxia stimulates
release of
erythropoietin by
kidneys

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 Hipoxia
Menit s/d jam (max : 24 jam)
Eritropoietin

Hambat

Sumsum tulang
Stem cells
Oksigenasi jaringan
Proeritroblast
5 hari

dipercepat

Eritrosit baru
(retikulosit meningkat)
30 – 50%

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 What is blood typing,
and why is it important?
What is the basis for ABO
and Rh incompatibilities?

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 Blood Grouping
 Determined by antigens (agglutinogens)
on surface of RBCs
 Antibodies (agglutinins) can bind to RBC
antigens, resulting in agglutination
(clumping) or hemolysis (rupture) of
RBCs
 Groups
 ABO and Rh

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Surface Antigens

 Are cell surface proteins that

identify cells to immune system
 Normal cells are ignored and
foreign cells attacked

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Blood Types

 Are genetically determined

 By presence or absence of RBC
surface antigens A, B, Rh

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What are Blood Types?
 Karl Landsteiner in the early 1900s. There are four types of
blood in the ABO system: A, B, AB, O.

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4 Basic Blood Types
 A (surface antigen A)
 B (surface antigen B)
 AB (antigens A and B)
 O (neither A nor B)

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Agglutinogens
 Antigens on surface of RBCs
 Screened by immune system
 Plasma antibodies attack (agglutinate)
foreign antigens

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 Agglutination Reaction

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Blood Plasma Antibodies
 Type A:
 type B antibodies
 Type B:
 type A antibodies
 Type O:
 both A and B antibodies
 Type AB:
 neither A nor B

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 Rh Blood Group
 First studied in rhesus monkeys
 Types
 Rh positive: Have these antigens present on
surface of RBCs
 Rh negative: Do not have these antigens
present
 Hemolytic disease of the newborn (HDN)
 Mother produces anti-Rh antibodies that cross
placenta and cause agglutination and
hemolysis of fetal RBCs

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 Hemolytic Diseases of Newborn

Matter11/8/2019
F, Saladin: Anatomy & Physiology: The UnityBlok
of Hematology Function, Third Edition, © The McGraw−Hill Companies, 33
Form and 2012-2013 2003
 Erythroblastosis Fetalis

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Cross-Reaction
 Also called transfusion reaction
 Plasma antibody meets its specific
surface antigen
 Blood will agglutinate and hemolyze
 If donor and recipient blood types not
compatible

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Cross-Reaction

Figure 19–6b
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 Effects of a Mismatched Transfusion

Matter11/8/2019
F, Saladin: Anatomy & Physiology: The UnityBlok
of Hematology Function, Third Edition, © The McGraw−Hill Companies, 37
Form and 2012-2013 2003
Blood Type Test
 Determines blood type and compatibility

Figure 19–7
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Cross-Match Test
 Performed on donor and recipient blood for
compatibility
 Without cross-match, type O— is universal
donor

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 Indri N. Rahayu, dr, MKes.

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White Blood Cells

 Leukocytes (leuko=white, cyte=cell)

 Contain of nuclei & organelles

 Attack pathogens & remove toxins, wastes,
& abnormal/damage cells
 A typical µL of blood contains 6000-9000
WBCs.
 Most in the connective tissues or in organs
of the lymphatic system

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 Leukocytes

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 White Blood Cells (Leukocytes)

 Divided into 2 groups:

 Granulocytes
○ Neutrophils
○ Eosinophils
○ Basophils
 Agranulocytes
○ Monocytes
○ Lymphocytes

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WBC Circulation and
Movement
 Do not circulate for extended periods of
time
 4 characteristics of circulating WBCs:
 Amoeboid movement
 Diapedesis
 Positive chemotaxis
 Phagocytosis

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WBC Circulation and Movement

 Characteristics of
circulating WBCs:

– Capable of amoeboid movement

– They can migrate out of the bloodstream by
squeezing thru endothelial cells (this process is
called diapedesis)
– They are attracted to specific chemical stimuli.
This is known as positive chemotaxis and
allows WBCs to converge on pathogens and
damaged tissues
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WBCs: General Functions
 Nonspecific defense
 Neutrophils
 Eosinophils
 Basophils
 Monocytes
 Specific defense
 Lymphocytes

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 Functions of Leukocytes
 WBC’s accumulate at sites of
infection/inflammation
◦ Lymphocytes recirculate between
blood and tissues
 Others remain in tissues
 WBC’s ‘emigrate’ from blood
compartment
◦ Adhesion molecules on WBC and
endothelial cells allow WBC’s to
‘stick’ to endothelium
 then move to site or
infection/inflammation via chemotaxis
 Once at site of infection /
inflammation WBC’s carry out
various functions in the
inflammatory / immune response
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Leukocyte Life Span and Number
 Life span determined by activity
 Ingesting foreign organisms, toxins, shortens
life
 Healthy WBC's – majority last days, but some
last months to years
 During infection, WBCs may only live hours
○ fill with ingested organisms, toxins, Ab-Ag
complexes
○ may die or burst

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Leukocyte Life Span and Number
 Life span of the leucocytes
 Granulocytes :
○ 4 - 8 hours in the blood circulation
○ 4 – 5 days in the tissues where they needed
 Monocytes :
○ 10 – 20 hours in the circulation before wandering
through the capillary membrane into the tissues
○ In the tissues, they swell to much larger sizes to
become tissue macrophages can live for
months unless destroyed while performing
phagocytic functions.
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Leukocyte Life Span and Number
 Lymphocytes :
◦ Weeks or months, depends the body’s need for
these cell
◦ Lymphocytes enter the circulatory system
continually, along with drainage of lymph from the
lymph nodes and other lymphoid tissue. After a few
hours, they pass out of the blood back into the
tissues by diapedesis. Then, still later, they re-enter
the lymph and return to the blood again and again;
thus, there is continual circulation of lymphocytes
through the body.

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Leukocyte Life Span and Number
 5,000 - 10,000 WBC’s/mm3 blood
 RBC/WBC ratio 700/1
 Differential WBC count (a standard clinical lab
report)
 Neutrophils 60-70%
 Lymphocytes 20-25%
 Monocytes 3-8%
 Eosinophils 2-4%
 Basophils 0.5-1%
 Abnormal proportions are correlated with
different types of disease processes
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 Monocyte-Macrophage Cell System
(Reticuloendothelial System)
 Tissue Macrophages in the Skin and
Subcutaneous Tissues (Histiocytes).
 Macrophages in the Lymph Nodes.
 Alveolar Macrophages in the Lungs.
 Macrophages (Kupffer Cells) in the Liver
Sinusoids.
 Macrophages of the Spleen and Bone Marrow.
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 Inflammation: Role of Neutrophils and
Macrophages

Inflammation is characterized by :
1. vasodilation of the local blood vessels, with
consequent excess local blood flow;
2. increased permeability of the capillaries,
allowing leakage of large quantities of fluid into
the interstitial spaces;
3. often clotting of the fluid in the interstitial spaces
because of excessive amounts of fibrinogen and
other proteins leaking from the capillaries;

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 Inflammation: Role of Neutrophils and
Macrophages

4. migration of large numbers of

granulocytes and monocytes into the
tissue; and
5. swelling of the tissue cells.

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 Inflammation: Role of Neutrophils and
Macrophages
 Some of the many tissue products that cause
these reactions are histamine, bradykinin,
serotonin, prostaglandins, several different reaction
products of the complement system, reaction
products of the blood clotting system, and multiple
substances called lymphokines that are released
by sensitized T cells.
 Several of these substances strongly activate the
macrophage system, and within a few hours, the
macrophages begin to demolish the destroyed
tissues.
 But at times, the macrophages also further
injure the still-living tissue cells.
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"Walling-Off" Effect of Inflammation
 One of the first results of inflammation is to "wall off"
the area of injury from the remaining tissues.
 The tissue spaces and the lymphatics in the inflamed
area are blocked by fibrinogen clots so that after a
while, fluid barely flows through the spaces.
 This walling-off process delays the spread of
bacteria or toxic products.
 The intensity of the inflammatory process is
usually proportional to the degree of tissue injury.

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"Walling-Off" Effect of Inflammation

 For instance, when staphylococci invade

tissues, they release extremely lethal
cellular toxins.
 As a result, inflammation develops rapidly-
indeed, much more rapidly than the
staphylococci themselves can multiply and
spread.
 Therefore, local staphylococcal infection is
characteristically walled off rapidly and
prevented from spreading through the
body.
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"Walling-Off" Effect of Inflammation

 Streptococci, in contrast, do not cause such

intense local tissue destruction.
 Therefore, the walling-off process develops
slowly over many hours, while many
streptococci reproduce and migrate.
 As a result, streptococci often have a far greater
tendency to spread through the body and cause
death than do staphylococci, even though
staphylococci are far more destructive to the
tissues.

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 Colony-Stimulating Factors (CSFs)
 Hormones that regulate blood cell
populations:
1. M-CSF:
 stimulates monocyte production

2. G-CSF:
 stimulates granulocyte production
 neutrophils, eosinophils, and basophils

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 Colony-Stimulating Factors (CSFs)

3. GM-CSF:
 stimulates granulocyte and monocyte
production

4. Multi-CSF:
 accelerates production of granulocytes,
monocytes, platelets, and RBCs

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Summary
 Blood is about 50% plasma, water solvent &
solutes: ions, elements, gasses, proteins,
wastes & nutrients
 Iron in hemoglobin is key to RBC transport of
O2
 Blood grouping is determined by antigens
(agglutinogens) on surface of RBCs
 Antibodies (agglutinins) can bind to RBC
antigens, resulting in agglutination (clumping)
or hemolysis (rupture) of RBCs
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Summary
 4 characteristics of circulating WBCs:
 Amoeboid movement
 Diapedesis
 Positive chemotaxis
 Phagocytosis
 Inflammation is characterized by :
Vasodilation, increased permeability of the
capillaries, often clotting of the fluid in the
interstitial spaces, migration of large numbers
of granulocytes and monocytes and swelling
of the tissue cells.
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 References
 Ganong WF, 2005. Review of Medical Physiology. 22nd
ed. New York: Lange Medical Books / McGraw-Hill
Medical Publishing Division
 Guyton AC and Hall JE, 2006. Textbook of Medical
Physiology. 11th ed. Philadelphia: WB. Saunders Co
 Matter F. 2003. Saladin: Anatomy & Physiology: The Unity
of Form and Function, 3rded. The McGraw−Hill Companies
 Widmaier EP, Raff H and Strang KT, 2004. Vander,
Sherman and Luciano’s Human Physiology : The
Mechanism of Body Function. 9th ed. McGraw-Hill
Publishing
 Fox EL, 2003. Human Physiology. 8th ed. McGraw-Hill
Publishing
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