BIOEN 345: Blood vessel biology

and pathologies

Lecture 2 April 27, 2020: Blood composition and

coagulation
Blood cells
Blood Cell Count
Hematocrit: ratio of red blood cells to plasma

Silverthorn Figure 16-3

Composition of Blood

Water 92%
Proteins 7%
Rest 1%

Silverthorn Figure 16-1 (1 of 2)

Composition of Blood -1

From nutrient absorption

(intestine to bloodstream)
or from cellular storage

From breakdown of amino

acids, nucleic acids
(mostly in form of urea)

O2 from breathing, CO2

waste product of
metabolism, removed via
respiration

Silverthorn Figure 16-1 (1 of 2)

Composition of Blood -2

60%

Transferrin

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 Deficiency of blood proteins
• Bleeding disorders:
– Hemophilia A (factor VIII) and B (factor IX). X-
linked
– Von Willebrand disease. Type I lower vWF,
type II abnormal vWF, no vWF
• Clotting disorders:
– Factor V Leiden mutation of factor V
– Deep vein thrombosis

• Infectious disease and coagulation

Composition of Blood

Silverthorn Figure 16-1 (2 of 2)

Silverthorn
 Production site

Rodak et al: Hematology: Clinical Principles and Applications, 2007

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Hematopoetic Cytokines

Molecular cell biology. Lodish, 2003

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 Production rate

• Platelets
• 1011 platelets are produced each day
• (150 – 400) × 103 per mm3.
• 5000 – 10000 platelets per Megs
• life span: 5-9 days
• Red blood cells
• 2.4 million new erythrocytes are produced per second (2 x
1011 RBCs per day)
• 2–3 × 1013 (20-30 trillion) red blood cells in our body at
one time
• life span: 120 days
• Leukocytes
• 7000 white blood cells per uL of blood (1%)
Cellular Elements: Leukocytes
• Phagocytes:
• Neutrophils
• Monocytes
• Eosinophils

• Lymphocytes

• Basophils

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 Immunity
• Ability to resist damage from foreign substances like
microorganisms and harmful chemicals
• Types
• Innate or nonspecific Immunity
• Mechanical mechanisms: Prevent entry or remove microbes
• Chemical mediators: Promote phagocytosis and inflammation
• Cells: Involved in phagocytosis and production of chemicals
• Adaptive or specific immunity
• Specific: Ability to recognize a particular substance
• Memory: Ability to remember previous encounters with a
particular substance and respond rapidly
Innate Immunity: Cells
Mechanism of Action • Macrophages
• Chemotaxis • Monocytes that leave
• Phagocytosis blood, enter tissues
• Neutrophils • Large phagocytic cells
• Phagocytic and first • Basophils and mast cells
cells to enter infected
• Promote inflammation
tissue
• Eosinophils
• Reduce inflammation
• Natural killer cells
• Lyse tumor and virus-
infected cells
Adaptive Immunity
• Involves the ability to recognize, respond to, and
remember a particular substance
• Stimulants
• Antigens: Large molecules
• Foreign: Not produced by body, introduced from outside
• Self-antigens: Produced by body
• Types
• Humoral or Antibody-mediated: B cells
• Cell-mediated: T cells
White Blood Cell Diseases
• Leukemia – Bone Marrow
o Acute lymphocytic leukemia (ALL)
o Chronic lymphocytic leukemia (CLL)
o Acute myeloid leukemia (AML)
o Chronic myeloid leukemia (CML)
• Lymphoma is a cancer that is found in the lymphatic
system - lymphomas are classified as B cell lymphoma
or T cell lymphoma.
• Myeloma is a cancer that develops from plasma cell -
the cancer is usually found in multiple areas of the
bone
Cellular Elements: Erythrocytes
• Red blood cells
• Contain no nucleus
• Live in circulation for ~ 4
months
• Contain a few enzymes and a
lot of hemoglobin
• Hemoglobin binds O2 molecules

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Fe Metabolism

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 Blood type
• The alleles (A, B, and O) code for glycoproteins on the surface of red blood cells

• If you receive blood that is not compatible with your own, your body triggers an
immune response against the foreign glycoproteins—How does this work?
— The immune response
causes the blood to clump,
or agglutinate, which clogs
blood vessels and kidney
tubules and can be fatal.

• Rh factor, or Rhesus factor, is another surface protein on red blood cells

• Your body either has the allele to make it (Rh+) or it doesnʼt (Rh-)
• Anyone can receive Rh- blood
• Those with Rh- blood can not receive donor Rh+ blood
• During pregnancy, Rh- moms that are carrying Rh+ babies make antibodies against
the babyʼs blood
Pathology of Erythrocytes
Anemias
 Pathology of Erythrocytes
• Sickle blood cells
– Genetic blood disorder
(mutation in hemoglobin gene)
Val-his-leu-thr-pro-glu-glu-
Val-his-leu-thr-pro-val-glu-

– Abnormal, rigid, sickle shape

– Treatment – transfusion/ BMT

http://www.cc.nih.gov/ccc/ccnews/nov99/ http://www.nhlbi.nih.gov/health/health-
topics/topics/sca/
Cellular Elements: Platelets

• Platelets
• Also known as
thrombocytes
• Contain no
nucleus
• Smaller than
RBCs and
considered only
“cell fragments”
• Critical role in
clot formation

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• Clot formation
and tissue
repair

Figure 16-10
 Primary Hemostasis: “Platelet Plug”
• Occurs prior to complete clot formation
• Activates cascade of events that lead to clot formation

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WATCH! http://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htm
von Willebrand factor (VWF)
VWF binds to collagen
 Activation and Aggregation

Platelets adhere through integrins, and release serotonin and thromboxane A2 =

vasoconstrictors
Release also platelet activating factor to recruit more platelets
 The Coagulation Cascade

Figure 16-12
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WATCH! http://www.hopkinsmedicine.org/hematology/Coagulation.swf and
http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=301&contentid=669&rptname=Research
 Primary hemostasis

• Clot formation
and tissue repair

Silverthorn Figure 16-10

 Secondary hemostasis

• Clot formation
and tissue repair

Silverthorn Figure 16-10

 Thrombocytopenias
Thrombocytopenia is defined as a platelet count of less than 150,000/mm3.
Thrombocytopenia is rarely the cause of bleeding unless the count is less than 50,000/mm3.

•Platelet Underproduction
•Decreased marrow production.
–Common causes include infections, drugs, radiotherapy, vitamin deficiency, or marrow
infiltration by tumor.

•Platelet Sequestration
•Hypersplenism from a variety of causes may result in platelet sequestration.
–Causes of Splenomegaly: Cirrhosis Heart failure Portal or hepatic venous thrombosis.
–Malignancies.

•Increased Platelet Destruction

•Platelet destruction results from various immune conditions
 Pathology of platelets
• Structural deficiency
• Gray platelet syndrome – alpha granules can not store
proteins and are not release at the site of injury
• dense granule deficiency – Hermansky-Pudlak
syndrome – improper storage in the granules

• Functional deficiency
• Bernard-Soulier syndrome (BSS)
• absence of GPIb complex for adhesion, giant platlets
• Scott syndrome
• signal transduction pathway defect and no exposure of
phosphatidylserine – important for thrombin activation and
fibrin formation
• Glanzmann thrombasthenia
• GPIIb-IIIa receptor for fibrinogen– aggregation
Reading: Simon et al, Platelet function defects, Haemophilia, 2008, 14, 1240