Blood

Dr Jaclyn Mann
[email protected]
HPP Unit (Room 209),
Doris Duke Medical Research Institute,
Medical School
Text book
 Overview
Overview
• Components of blood: plasma, cells,
platelets
• Red blood cells:
- Characteristics and function
- Erythropoeisis
- Anaemia
- ABO and Rhesus blood groups
• White blood cells: types and functions
• Platelets: function
• Blood clotting and anticoagulants
 Blood – definition and
function
• Blood – variety of cells suspended in fluid (plasma)
• Travels in a system of vessels from and to the heart

Functions:
1. Transport of gases, nutrients, metabolic
waste products, cells and hormones
2. Regulation of temperature, pH, water
content + hormones regulate growth,
reproduction, mood, digestion etc.
3. Defence from infectious agents by the
white blood cells and defence from blood
loss through clotting
 Blood composition

• Plasma, cells (red blood cells, white blood

cells), platelets

55%
<1%

45%
haematocrit
 Plasma

• Water and dissolved solutes:

- Ions (mostly Na+)
- Nutrients
- Metabolic waste products
- Hormones
- Enzymes
- Antibodies
- Proteins
 Plasma Proteins
• Normally not taken up by cells, function is in the plasma
or interstitial fluid

• 3 groups: 1. Albumins, 2. globulins, 3.fibrinogen

• 1. Albumins: most abundant, produced by liver,

essential to provide osmotic pressure to maintain
blood volume, carrier protein for fatty acids and
hormones
 Plasma Proteins
• 2. Globulins

- α and β: transport lipids and fat soluble vitamins (liver)

- γ : antibodies produced by B-lymphocytes (WBCs)

defend against bacteria and viruses
 Plasma Proteins

• 3. Fibrinogen
- Important clotting factor produced by liver
- Fibrinogen fibrin threads (insoluble)
Plasma Volume Regulation

Plasma volume decrease

Increased osmolality

Osmoreceptors

Thirst and antidiuretic hormone released

Water retention by kidneys

Red blood cells (erythrocytes)

2.2μm
 Red blood cells
• 4-6 million RBCs per cubic mm of blood

• Major function = transport oxygen from lungs to tissues

• Characteristics relating to its function:

1. Each RBC carries ≈ 280 million haemoglobin molecules
(combine with oxygen)
2. Biconcave disc shape = high surface area to volume ratio, can
squeeze through capillaries, flexible.
3. Lack nuclei (more space for haemoglobin) – means it cannot
reproduce – lifespan ≈ 120 days (removed in spleen, liver, BM)
4. Lack mitochondria – anaerobic metabolism (don’t use oxygen)
 Haemoglobin

Haemoglobin = 4 globin protein

chains and 4 haeme molecules (iron-
containing)

• Iron (bound to haeme) binds and releases O2

• Source of iron for RBC production = recycling from old

RBCs + diet (small amount required)

• Transferrin (beta-globulin) transports iron in blood

 Anaemia
• Low RBC or low haemoglobin
- Iron-deficiency
- Pernicious (low vitamin B12 low RBC production)
- Aplastic (bone marrow damage, chemical/radiation)
- Sickle cell (hereditary, mutated haemoglobin,
crystallises at low O2, sickle shaped RBC, fragile, short-lived)
 Haematopoeisis
Stem cell
is the
precursor Erythropoeisis
of all the
blood Leukopoeisis
cells
The bone marrow
(myeloid tissue)
produces all of the
different types of blood
cells; the lymphoid
tissue produces
lymphocytes derived
from cells that
originated in the bone
marrow.
 Erythropoeisis
Required:
• Production of red blood cells 1. Iron
 the body must produce about 2.5 million 2. Vit B12
3. Folic acid
new RBCs every second (why?)
 in adults, erythropoiesis occurs mainly in
the marrow of the sternum, ribs,
vertebral processes, and skull bones
 rate is regulated by oxygen levels:
 hypoxia (lower than normal oxygen
levels) is detected by cells in the
kidneys
 kidney cells release the hormone
erythropoietin into the blood
 erythropoietin stimulates
erythropoiesis by the bone marrow
Blood groups and
transfusions
 Blood groups and
transfusions
• Transfusions in 1800’s – some recipients cured, some
died due to incompatibility of blood types (clumping of
RBCs and kidney failure).

• Many different surface antigens on RBCs may determine

compatibility between blood types.

• However, most important are the antigens of the ABO

group and Rhesus (Rh) factor group. Only
incompatibility of these antigens are likely to cause
serious transfusion reactions.
 ABO blood groups

• Based on 2 major antigens – A and B.

 ABO blood groups
• The corresponding antibody is absent if the antigen is
present
 Transfusion reactions

• A reaction if the antibodies in the

recipients plasma recognise the antigen
on the donor cells – destroy donor cells

• Note that the antibodies in the donor plasma could also

destroy recipient RBC with the same antigen but this is
negligible due to dilution
(recipients larger blood volume dilutes donor blood)
 Transfusion reactions
• If types mismatched, recipients antibodies attach to
donor RBCs and form bridges - agglutination
 Transfusion reactions

Recipient type Preferred Donor Permissible donor

type type in emergency

A A O

B B O

AB AB A,B,O

O O Only O

AB = universal recipient
O = universal donor
 Question
• Can a person with type A blood receive a
donation of type AB blood?
Explain why you say yes or no.
 Rh group
• Named after rhesus monkey in which it was discovered

• Many different antigens in this group, D is of significance

• Rh positive (D present), Rh negative (D absent)

• Rh positive by far the most common

• Transfusion significance:
Rh –ve person makes antibodies to Rh antigen following
transfusion with Rh +ve blood = sensitised
Next transfusion – likely agglutination, adverse reaction
 Rh group – erythroblastosis
fetalis
• Haemolytic disease of the newborn (Rh –ve mother, Rh
+ve fetus)
White blood cells - leukocytes
Iron regulation

• Nuclei, mitochondria, lack haemoglobin, amoeboid motion (can

move out of capillaries to site of infection – diapedesis/
extravasation)
pink blue neutral,
polymorphonuclear

Agranular Granular (granulocytes)

White blood cells - leukocytes
Iron regulation

• typical concentration is 5000 - 10000 per cubic millimeter

of circulating blood
• neutrophils (54-62% of circulating WBCs)
• eosinophils (1-3%)
• basophils (less than 1%)
• lymphocytes (25-33%)
• monocytes (3-9%)
• Most WBCs are in tissues, small fraction in circulation
• help defend the body against invasion by pathogens,
and remove abnormal or damaged cells.
White blood cells - leukocytes
Iron regulation

• Can move out of blood stream in response to chemical

stimuli, which guide WBCs to invading pathogens,
damaged tissue and other activated WBCs.

• Some leukocytes (neutrophils, eosinophils and

monocytes) can perform phagocytosis of pathogens and
cell debris. Macrophage is a monocyte moved out of bloodstream
and actively phagocytic.

• 1. Non-specific defenses (innate immunity) – neutrophils,

eosinophils, basophils monocytes
2. Specific defenses (adaptive immunity) - lymphocytes
 Neutrophils
54-62%
• First WBCs to arrive at an infection site or injured site

• Attracted by chemical stimuli (bacterial/viral toxins, and

products of infected/inflamed tissue) to such sites.
Move towards chemical stimulus = chemotaxis

• Squeeze through pores in blood vessel walls = diapedesis

• Phagocytose cell debris and pathogens.

 Neutrophil granules
• Engulfed particle/pathogen is in internal vesicle
(phagosome) which then fuses with cytoplasmic granules
(lysosomes)

• 3 main types of granules

– Azurophil granules = primary (acid hydrolases to digest
ingested material and microbicidal substances to kill
ingested bacteria e.g. myeloperoxidases)
– Specific granules = secondary (inflammatory mediators
and antimicrobial substances)
– Small storage granules = tertiary (secrete enzymes to
break down damaged tissue, e.g. gelatinase breaks
down damaged collagen)
 Monocytes, Macrophages
3-9%

• Monocytes have large, eccentrically placed, bean-

shaped nucleus

• Monocytes enter tissues, increase in size and develop

large numbers of granules (lysosomes) = macrophages
with powerful phagocytic ability

• Like neutrophils, macrophages phagocytose tissue

debris and microbes (digest and kill within granules, half
of which resemble primary granules of neutrophils)
 Monocytes, Macrophages

• Monocytes attracted by chemotaxis to inflamed tissues

where differentiate into macrophages (↑ numbers)

• Usually circulate for ≈3 days and then enter tissues to

replenish resident macrophages (protective function):
 Kupffer cells of the liver
 Microglia of the CNS
 Langerhans cells of the skin
 Alveolar macrophages in lung
 Antigen-presenting cells of the lymphoid organs
 Eosinophils
• Circulate for 8-12 hours, enter tissues - under 1-3%
normal conditions found in the spleen, lymph nodes
and gastrointestinal tract where survive for several days

• Move into tissues in response to inflammatory or allergic

responses

• Increase in tissues in which allergic reactions have

occurred:
- mast cells and basophils participate in allergic reactions and release
eosinophil chemotactic factor

- Eosinophils detoxify some inflammation-inducing substances and

phagocytose allergen-antibody complexes
 Eosinophil
Major function- respond to parasitic infections (increase in
numbers in people with parasitic infections)

Weak phagocytic activity but:

• Large specific granules

– Major basic protein
– Hydrolytic enzymes
– Peroxidase

Attach to the juvenile parasite

• Release hydrolytic enzymes from their granules
• Release of highly active forms of O2 that are lethal
• Release highly larvacidal polypeptide –major basic protein
 <1%
Basophils

• Basophils have many structural and functional

similarities with mast cells (tissue).

• Both cells release heparin into blood - anticoagulant

• Central role in inflammatory and immediate allergic

reactions

• Cytoplasmic granules store mediators of inflammation

e.g. histamine, serotonin, prostaglandin
 Basophils

Allergic reactions:
• IgE antibody attaches to mast cells and basophils

• Specific antigen (allergen) binds to specific IgE antibody

• Mast cell or basophil ruptures

• Releases histamine (vasodilation, increased vascular

permeability) bradykinin, serotonin, heparin, slow reacting
substance of anaphylaxis (spasm of bronchiolar smooth
muscle) = allergic manifestations
 Lymphocytes
25-33%
• Large nucleus, little cytoplasm, smallest of WBCs but size
increases when activated by foreign antigen

• Lymphocytes play the central role in all immunological

defence mechanisms, provide specific immune response
• B lymphocytes produce antibodies when activated
• T lymphocytes can destroy infected cells

• Lymphocytes produced in bone marrow but may undergo

further development and division elsewhere (e.g. thymus)

• They migrate to lymphoid tissue (lymph nodes, spleen,

tonsils, lymphoid follicles in gastrointestinal tract) encounter
foreign antigen
 White blood cells – function
Iron regulation
summary slide
1. Neutrophil
2. Monocyte (becomes macrophage when enters tissues)
1+2 enter injured or infected tissues, engulf damaged tissue and bacteria

3. Eosinophils – important in parasitic infections

4. Basophils – mediate allergic reactions

5. Lymphocytes – provide specific defense against viruses and bacteria .

Recognises a specific pathogen and forms memory to it. On reinfection with the same
pathogen will be able to mount a strong immune response quickly
 Leukopoeisis

• Cytokines stimulate various stages of leukocyte

production and the production of specific leukocytes

• Granulocyte stimulating colony factor (G-SCF) stimulates

neutrophil production

• Granulocyte-monocyte stimulating colony factor (GM-SCF)

stimulates monocyte and eosinophil production

• Interleukin-3, for example, has more general effects

promoting the production of different WBC types
 Platelets - thrombocytes
• Small, non-nucleated, formed in the bone marrow following
fragmentation of cells called megakaryocytes

• 130 000 to 400 000 per cubic mm of blood, 5-9 days

• Play an important role in cessation of bleeding

(haemostasis) following injury and blood clotting

• Secrete growth factors important in maintaining blood

vessel integrity and for wound healing
 Platelets - thrombocytes
• Thrombopoietin promotes proliferation of megakaryocytes and
their development into platelets

• Megakarocytes and platelets bind thrombopoietin

• Therefore, when platelet count is low, there is increased free

thrombopoietin which can stimulate megakaryocytes

• When the platelet count is high, there is decreased free

thrombopoieten and decreased stimulation of megakaryocytes

• Synthesised thrombopoietin can be used to treat low platelet

count
 Haemostasis and blood clotting
Haemostasis- cessation of bleeding

Breaking the endothelial lining of a blood vessels 3

haemostatic effects:

• Vasoconstriction (nervous reflex, few minutes, aided by platelets)

• Platelet plug formation
• Fibrin network formation that surrounds and penetrates the
platelet plug = blood clotting (formation of fibrin)
 Platelet plug formation
• Intact blood vessel (b/v), platelets repelled by b/v endothelium
and each other

• Endothelium= layer of cells overlying collagen

• Endothelium secretes prostacyclin, nitric oxide, and CD39

(converts ADP to AMP) = protective mechanisms preventing
platelet activation

• Vessel endothelium is broken, platelets bind to collagen

• Von Willebrand’s factor (endothelium) binds platelets and

collagen preventing platelets being pulled off collagen by blood
flow
 Platelet plug formation
• Platelets degranulate releasing ADP, serotonin and thromboxane
A2 (Thromboxane A2 helps maintain vasoconstriction)

• ADP and thromboxane A2 released recruit new platelets which

stick to the platelets attached to the collagen

• The second layer undergoes platelet release reaction and a

platelet plug is formed in the damaged vessel

• Activated platelets help activate plasma clotting factors that convert

fibrinogen to fibrin

• Platelets membrane has binding site for fibrinogen and fibrin

which help strengthen platelet plug
Platelet plug formation

Blood clots
contain
platelets and
fibrin and
trapped RBCs
 Clotting: formation of fibrin
Fibrinogen→Fibrin

Intrinsic Extrinisic

Activators: Collagen, Glass Activators: Tissue thromboplastin

Prothrombin
inactive glycoprotein

Thrombin enzyme

Fibrinogen soluble

Fibrin monomers

Fibrin polymers insoluble

Clotting factors: Roman numerals

I II III IV V VI VII VIII IX X XI XII

1 2 3 4 5 6 7 8 9 10 11 12
Clotting: intrinsic and extrinsic

(III)
Dissolution of Clots + Anticoagulants

• Activated factor XII promotes formation of plasmin by

series of reactions
• Plasmin dissolves clot

• Anticoagulants:

- EDTA chelates Ca2+ prevent clotting in test tubes

- heparin inactivates thrombin, given during surgery

- coumarins e.g. warfarin, vitamin K needed for proper

function of certain clotting factors, warfarin blocks activation
of vitamin K
• Explain regulation of the plasma volume.
[3]
• What condition might an increase in
eosinophils indicate? Explain your
answer. [1]
• Explain how coumarin drugs, EDTA, and
heparin function as anticoagulants. [3]
Complete the following table to indicate whether the listed
characteristics are present or not present in erythrocytes and
leukocytes. [4]

Characteristic Erythrocytes Leukocytes

Nucleus
present
Mitochondria
present
Haemoglobin
present
Amoeboid
motion
• Production of which of the following blood
cells is stimulated by a hormone secreted
by the kidneys?
• a. Lymphocytes
• b. Monocytes
• c. Erythrocytes
• d. Neutrophils
• e. Thrombocytes
• Platelets
• a. form a plug by sticking to each other.
• b. release chemicals that stimulate
vasoconstriction.
• c. provide phospholipids needed for the
intrinsic pathway.
• d. serve all of these functions.