THE CIRCULATORY SYSTEM: BLOOD

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THE CIRCULATORY SYSTEM BLOOD
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TABLE OF CONTENT
1) Overview of the circulatory system 2) The
blood Plasma The Formed Elements - Erythrocytes -
Human Blood Groups - Leukocytes - Hemostasis


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Overview of the circulatory system
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The circulatory system is composed of
1) the blood (the circulating material) 2) the
heart (pump) 3) blood vessels (conduit)
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The circulatory system
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Why is cardiovascular system needed?
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Life evolved from oceans.
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Nutrients
cell
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Nutrients
cell
cell
cell
cell
cell
cell
cell
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Nutrients
cell
cell
cell
cell
cell
cell
cell
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Internal environment
the interstitium
cell
cell
cell
cell
cell
cell
cell
External environment
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Constant (homeostasis)
Goal
H2O Glucose Lipids Amino acids Vitamins Minerals O
2 pH 7.35-7.45 38 C 290 mOsm
cell
cell
cell
cell
cell
cell
cell
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External Environment
H2O Glucose Lipids Amino acids Vitamines Minerals
O2 pH 7.35-7.45 38 C 290 mOsm
Digestive
Respiratory
Blood
Respiratory Urinary
All tissue cells
Urinary
Endocrine Neural
Interstitium
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• Primary Functions of the Circulatory System
•  
• 1) Transportation  
• Deliver life-supporting materials, i.e., O2,
  glucose, amino acid, fatty acids, vitamins,
  minerals, etc.

• Deliver regulating signals, i.e., hormones to
  tissue cells

• - Collect waste products from tissue cells and
  deliver to special organs (kidney, lung) for
  disposal

- Distribute heat throughout the body
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Primary Functions of the Circulatory System   2)
Protection - Special components of the blood
patrol the whole body and fight against invaded
microorganisms and cancerous cells.
H2O Glucose Lipids Amino acids Vitamins Minerals O
2 pH 7.35-7.45 38 C 290 mOsm
cell
cell
cell
cell
cell
cell
cell
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The Blood
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Composition of the Blood
1) Plasma 2) The Formed Elements (blood
cells/cell fragments)
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General Properties of Whole Blood - Fraction
of body weight - Volume - temperature -
pH 7.35 - 7.45 - Viscosity (relative to
water) - Osmolarity - Mean salinity
(mainly NaCl)
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Female 4-5 L Male 5-6 L
38? C (100.4? F)
Whole blood 4.5-5.5 plasma 2.0
280-300 mOsm/L
0.85
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Hematocrit RBCs as percent of total blood
volume
100
- Female 37-48 - male 45-52
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General Properties of Whole Blood (continued)
Hemoglobin Female 12-16 g/100 ml male
13-18 g/100 ml Mean RBC count Female 4.8
million/?l male 5.4 million/?l Platelet
counts 130,000-360,000/?l Total WBC
counts 4,000-11,000/?l
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Plasma
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Composition of Plasma
Water 92 by weight Proteins Total 6-9
g/100 ml Albumin 60 of total plasma
protein Globulin 36 of total plasma
protein Fibrinogen 4 of total plasma
protein Enzymes of diagnostic value trace Glucose
(dextrose) 70-110 mg/100 ml Amino
acid 33-51 mg/100 ml Lactic acid 6-16
mg/100 ml
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Composition of Plasma (continued)
Total lipid 450-850 mg/100 ml Cholesterol 12
0-220 mg/100 ml Fatty acids 190-420 mg/100
ml High-density lipoprotein (HDL) 30-80 mg/100
ml Low-density lipoprotein (LDL) 62-185 mg/100
ml Neutral Fats (triglycerides) 40-150 mg/100
ml Phospholipids 6-12 mg/100 ml
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Composition of Plasma (continued)
Iron 50-150 ?g/100 ml Vitamins (A, B, C, D,
E, K) Trace amount Electrolytes Sodium 135-145
mEq/L Potassium 3.5-5.0 mEq/L Magnesium 1.3-2.1
mEq/L Calcium 9.2-10.4 mEq/L Chloride 90-106
mEq/L Bicarbonate 23.1-26.7 mEq/L Phosphate 1.4-
2.7 mEq/L Sulfate 0.6-1.2 mEq/L
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Composition of Plasma (continued)
Nitrogenous Wastes Ammonia 0.02-0.09 mg/100
ml Urea 8-25 mg/100 ml Creatine 0.2-0.8
mg/100 ml Creatinine 0.6-1.5 mg/100 ml Uric
acid 1.5-8.0 mg/100 ml Bilirubin 0-1.0
mg/100 ml Respiratory gases (O2, CO2, and N2)
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plasma
serum
clotting proteins (fibrin)
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The Formed Elements (Blood Cells)
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 Formed elements include  Erythrocytes (red
blood cells, RBCs) Platelets (cellular
fragments) Leukocytes (white blood cells,
WBCs) Granulocytes Agranulocytes
Neutrophils Eosinophils Basophils
Lymphocytes Monocytes
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Erythrocytes (red blood cells)
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Erythrocytes (Red Blood Cells, RBCs)
Appearance - biconcave disc shape, which is
suited for gas exchange. The shape is flexible
so that RBCs can pass though the smallest blood
vessels, i.e., capillaries.
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Erythrocytes are smaller than Leukocytes.
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Erythrocytes (Red Blood Cells, RBCs)

• Structure
• Primary cell content is hemoglobin, the protein
  that binds oxygen and carbon dioxide.
• no nucleus nor mitochondria

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Hemoglobin consists of globin and heme
pigment
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Globin - Consists of two ? and two ? subunits -
Each subunit binds to a heme group
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Heme Groups
Each heme group bears an atom of iron, which
binds reversibly with one molecule of oxygen
Heme Group Structure
carry four molecules of oxygen
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Carbon monoxide competes with oxygen for heme
binding with a much higher affinity.
Problem
deoxygenate hemoglobin
Treatment
hyperbaric oxygen chamber
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Oxyhemoglobin - bound with oxygen - red
Deoxyhemoglobin - free of oxygen - dark red.
Carbaminohemoglobin 20 of carbon dioxide in
the blood binds to the globin part of hemoglobin,
which is called carbamino-hemoglobin.
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Functions of Erythrocytes
1) Primary Function Transport oxygen from the
lung to tissue cells and carbon dioxide from
tissue cells to the lung
2) Buffer blood pH
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Production of Erythrocytes
Hematopoiesis refers to whole blood cell
production. Erythropoiesis refers specifically
to red blood cell production.
All blood cells, including red and white, are
produced in red bone marrow. On average, one
ounce, or 100 billion blood cells, are made each
day.
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Hematopoiesis

• The red bone marrow is a network of reticular
  connective tissue that borders on wide blood
  capillaries called blood sinusoids. As
  hemocytoblasts mature, they migrate through the
  thin walls of the sinusoids to enter the blood.

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All of blood cells including red and white arise
from the same type of stem cell, the
hematopoietic stem cell or hemocytoblast
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Erythropoiesis
Erythrocytes are produced throughout whole life
to replace dead cells.
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Feedback Regulation of Erythropoiesis
- regulated by renal oxygen content. -
Erythropoietin, a glycoprotein hormone, is
produced by renal cells in response to a
decreased renal blood O2 content. -
Erythropoietin stimulates erythrocyte production
in the red bone marrow.  
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  A drop in renal blood oxygen level can result
from   1) reduced numbers of red blood cells
due to hemorrhage or excess RBC destruction.

1. reduced availability of oxygen to the blood, as
   might occur at high altitudes or during pneumonia.

3) increased demands for oxygen (common in those
who are engaged in aerobic exercise).
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Ways to increase Red Blood Cell Count in Sports

• Legal
• Illegal

raise RBC count by training athletes at high
altitude
use erythropoietin, androgen, or their analogs
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Dietary Requirements for Erythropoiesis Iron vi
tamin B12 folic acid More important to women
due to the loss of blood during menstruation
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The average life span of erythrocytes is 120
days.
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Erythrocyte Disorders
Anemia is a condition in which the blood has an
abnormally low oxygen-carrying capacity.  
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• Common causes of anemia include
• an insufficient number of red blood cells
• 2) decreased hemoglobin content
• 3) abnormal hemoglobin
• Two such examples are Thalassemias and
  Sickle-cell anemia, which are caused by genetic
  defects.

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Erythrocyte Disorders - 2
Polycythemia is an abnormal excess of
erythrocytes that increases the viscosity of the
blood, causing it to sludge or flow sluggishly.

• Common causes of polycythemia include
• Bone marrow cancer
• A response to reduced availability of oxygen as
  at high altitudes

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Human Blood Groups
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Human Blood Groups
- were learned from tragedies (death) caused by
mismatch during transfusion in ancient time. -
ABO blood types were identified in 1900 by Karl
Landstein (1930 Nobel laureate). - Other blood
types were identified later.
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Blood type is determined by

• Agglutinogens
• are specific glycoproteins on red blood cell
  membranes.
• All RBCs in an individual carry the same
  specific type of agglutinogens.

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ABO Blood Groups
Type A RBCs carry agglutinogen A. Type B RBCs
carry agglutinogen B. Type O RBCs carry no A
nor B agglutinogens. Type AB RBCs carry both A
and B agglutinogens.
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Type A blood

•  
• RBCs carry type A agglutinogens.
• - Plasma contain preformed antibodies,
• Agglutinin B, against B agglutinogens.
•  

A
A
A
A
A
A
A
B
A
B
B
B
B
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Agglutinins - are preformed antibodies in
plasma - bind to agglutinogens that are not
carried by host RBCs - cause agglutination ---
aggregation and lysis of incompatible RBCs.
Agglutinin B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
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Mix Type A plasma with Type B RBCs
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
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Type B recipient
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Type B blood
B

• RBCs carry type B agglutinogens.
• - Plasma contain agglutinin against A
  agglutinogens.
•  

B
B
A
B
B
A
B
B
B
B
A
A
A
A
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Type O blood
- RBCs carry neither type A nor type B
agglutinogens. - Plasma contain agglutinin
against both A and B agglutinogens. - The person
can accept only type O blood transfusion.
A
A
B
B
B
B
A
A
A
A
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Type AB blood
Agglutinogen(s) ? Agglutinin(s) ?
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Type AB blood
Agglutinogen(s)
A and B
A
B
No A nor B
Agglutinin(s) ?
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Summary of ABO Blood Groups
Blood Type Agglutinogen (on RBC) Agglutinin (in Plasma)
A A B
B B A
O A B
AB A B
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Blood Type Match
A B O AB
A Yes No Yes? No
B No Yes Yes? No
O No No Yes No
AB Yes? Yes? Yes? Yes
D
R
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Case Study

• A person lost 50 (3 liter) of his type-A blood.
• There is only type-O blood available for
  transfusion.
• Questions
• Can transfusion with 3 liters of type O blood
  cause any problem?

2) If can, what is the problem?
A
O
3) How to solve the problem?
recipient
donor
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Rh Blood Groups
Classify blood groups based on Rh agglutinogens
other than A/B agglutinogens
Rh positive - RBCs contain Rh agglutinogens.
Rh
A
Rh
A
A
Rh
Rh
A
- The majority of human beings is Rh positive.
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• Rh negative
• - The RBCs contain no Rh agglutinogens.
• Agglutinins against Rh-positive RBCs are
  produced after Rh-negative blood sees
  Rh- positive RBCs.

A
Rh
A
A
Rh
Rh
A
Rh
Rh
A
Rh
A
B
A
A
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The problem with a Rh-negative mother and her
Rh-positive fetus.
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First Preganancy
no anti-Rh
Protected by the placenta-blood barrier, the
mother is not exposed to Rh agglutinogens until
the time of childbirth due to placental tearing.
no Rh
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Generation of anti-Rh agglutinins
anti-Rh agglutinins
no Rh
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Born with severe anemia
Treatment use anti-Rh ? globulin to mask Rh
agglutinogens
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Leukocytes (White Cells)
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•  Leukocytes are grouped into two major
  categories
• Granulocytes
• - contain specialized membrane-bound cytoplasmic
  granules
• - include neutrophils, eosinophils, and
  basophils.
• Agranulocytes
• - lack obvious granules
• - include lymphocytes and monocytes

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Leukocytes (WBCs) Count
4,000-11,000 / ?L
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Function of Leukocytes defense against
diseases
Leukocytes form a mobile army that helps protect
the body from damage by bacteria, viruses,
parasites, toxins and tumor cells.
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Primary Functions of the Circulatory System   2)
Protection.
H2O Glucose Lipids Amino acids Vitamins Minerals O
2 pH 7.35-7.45 38 C 290 mOsm
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Leukocytes circulate in the blood for various
length of time.
Life span - several hours to several days for
the majority - many years for a few memory cells

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Neutrophils

• 40-70 WBCs
• Nucleus multilobed
• - Duration of development 6-9 days
• - Life Span 6 hours to a few days
• - Function phagocytize bacteria

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Eosinophils

• 1-4 WBCs
• Nucleus bilobed
• - Development6-9 days
• Life Span 8-12 days
• Function
• 1) Kill parasitic worms
• 2) destroy antigen-antibody complexes
• 3) inactivate some inflammatory chemical of
  allergy

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Basophils

• 0.5 WBCs
• Nucleus lobed
• - Development 3-7 days
• - Life Span a few hours to a few days
• - Function
• 1) Release histamine and other mediators of
  inflammation
• 2) contain heparin, an anticoagulant

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Lymphocytes

• - T cells and B cells
• 20-45 WBCs
• Nucleus spherical or indented
• - Development days to weeks
• - Life Span hours to years
• Function
• Mount immune response by direct cell attack (T
  cells) or via antibodies (B cells)

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Monocytes

• 4-8 WBCs
• Nucleus U-shaped
• - Development 2-3 days
• - Life Span months
• Function
• Phagocytosis
• develop into macrophages in tissues

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Leukocytes are deployed in the infected areas
outside blood vessels via 3 steps.

1. Margination
2. Diapedesis
3. chemotaxis

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Leukocytes are deployed in the infected areas
outside blood vessels via 3 steps.

1. Margination

slow down by cell adhesion molecules secreted by
endothelial cells
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• Diapedesis
• Leukocytes slip out of the capillary blood
  vessels.

Blood Capillary
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3) Chemotaxis Gather in large numbers at
areas of tissue damage and infection by following
the chemical trail of molecules released by
damaged cells or other leukocytes
Blood Capillary
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Phagocytosis Destroy foreign substances or dead
cells
Blood Capillary
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Leukocyte Disorders
Normal Leukocyte Count 4,000
11,000/?l   Leukopenia lt 4,000/?l normal
leukocytes Leukocytosis gt 11,000/?l normal
leukocytes  
Leukopenia is one major side effect of
chemotherapy.
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Why Leukopenia during chemotherapy?
- Cancerous cells grow fast, which distinguish
themselves from most of normal cells. -
Chemotherapy is designed to kill fast-growing
cells by interrupting mitotic cell division. -
Chemotherapy also kills a few normal fast-growing
cells including
leukocytes
hair
intestinal epithelial cells
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Leukemia - Leukemia refers to a group of
cancerous conditions of white blood cells. -
Descendants of a single stem cell in red bone
marrow tend to remain unspecialized and mitotic,
and suppress or impair normal bone marrow
function. - extraordinarily high number of
abnormal (cancerous) leukocytes
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HEMOSTASIS
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• HHemostasis refers to the stoppage of bleeding.
• Hemostatsis Homeostasis
• Maintaining balance
•  
• TThree phases occur in rapid sequence.

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1) vascular spasms
3)     blood clotting / coagulation
2)   platelet plug formation
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PPlatelets
Platelets are not cells but cytoplasmic fragments
of extraordinarily large (up to 60 ?m in
diameter) cells called megakaryocytes. Normal
Platelet Count 130,000 400,000/?l  
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Function of Platelets 1) Secrete
vasoconstrictors that cause vascular spasms in
broken vessels
vascular spasms
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2) Form temporary platelet plugs to stop bleeding
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3) Secrete chemicals that attract neutrophils
and monocytes to sites of inflammation
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4) Secrete growth factors that stimulate mitosis
in fibroblasts and smooth muscle and help
maintain the linings of blood vessels
5) Dissolve blood clots that have outlast their
usefulness
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Coagulation (Clotting)

• Many clotting factors in plasma are involved in
  clotting.
• These factors are inactive in the blood.
• They are activated when
• blood vessel is broken, or
• blood flow slows down.

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• The sequential activation (reaction cascade) of
  the clotting factors finally leads to the
  formation of fibrin meshwork.
• - Blood cells are trapped in fibrin meshwork to
  form a hard clot.

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Fibrin Polymer
Fibrinogen
Fibrin
soluble monomer
Insoluble filaments
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Coagulation Disorders   Thrombosis is the
abnormal clotting of blood in an unbroken
vessel.   Thrombus is a clot that attaches to the
wall of blood vessel.   Embolus is a clot that
comes off the wall of blood vessel and travel in
the blood stream. Embolism is the blockage of
blood flow by an embolus that lodges in a small
blood vessel. Infarction refers to cell death
that results from embolism. Infarction is
responsible for most strokes and heart attacks.
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Bleeding Disorders
1) Thrombocytopenia - the number of
circulating platelets is deficient (lt50,000/?l
) - causes spontaneous bleeding from small blood
vessels all over the body   2) Deficiency of
clotting factors due to impaired liver
function   3) Hemophilias hHereditary bleeding
disorders due to deficiency of clotting factors
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SUMMARY
1) Overview of the circulatory system 2) The
blood Plasma The Formed Elements - Erythrocytes -
Human Blood Groups - Leukocytes - Hemostasis