2. • Plasma volume
• Blood volume
• plasma composition & function
• blood composition & cell count
• White blood cell types & function
• Platelets count & function
• Hemostasis, mechanism &
disorders
Lecture Outline
3. blood consists of 3 types of
specialized cellular elements:
erythrocytes(RBC) Whole cells
leukocytes(WBC) whole cells
Platelets(thrombocytes) Cell
fragments
suspended in a complex liquid
plasma
4.
5.
6. packed cell volume(PCV):
the fraction of the blood composed of red blood cells
determined by centrifuging
men=0.40
women=0.36
severe anemia= 0.10
Polycythemia= 0.65
7. Measuring plasma volume:
serum albumin labeled with radioactive
iodine (125I-albumin).
Evans blue dye (T-1824)
9. Measuring blood volume
Another way: inject into the circulation red
blood cells that have been labeled with
radioactive chromium (51Cr).
10. The average blood volume of adults is about
7% of body weight , or about 5 liters.
60 % :plasma
40% :RBC’S
these percentages differ, depending on
gender, weight, and other factors.
11.
12. 3 liters.
the noncellular part of the blood
it exchanges substances continuously with
the interstitial fluid through the pores of the
capillary membranes.
These pores are highly permeable to all
solutes except proteins
13. Composition:
contains large amounts of sodium and chloride
ions, reasonably large amounts of bicarbonate
ions.
but only small quantities of potassium,calcium,
magnesium, phosphate, and organic acid ions.
The composition of plasma is regulated by the
kidneys.
14. The largest portion of the blood
90% water.
Water is a medium for materials being carried
in the blood , & can absorb and distribute
heat
15. Inorganic constituants :
1% of plasma weight
Most abundant ions in plasma Na⁺,Cl⁻
HCO₃⁻,K⁺, Ca⁺² in smaller amounts
They function in:
membrane excitability
osmotic distribution of fluid between Extracelluar fluid and cells
buffering of pH changes.
17. Plasma protiens functions
maintain plasma volume
Partially responsible for buffering pH .
Bind substances that poorly dissolve in plasma ( thyroid hormone
, cholesterol , iron)
Blood clotting factors are plasma protiens
Inactive circulating precursor molcules
(ex:angiotensinogenangiotensin).
Gamma globulins are immunoglobulins (antibodies)which are
crucial to body defence mechanism.
18.
19.
20.
21. Function:
transport hemoglobin, which in turn carries
oxygen
contain carbonic anhydrase,
Acid-Base buffer( by hemoglobin)
22. biconcave discs
diameter of about 7.8 micrometers and a thickness of
2.5 micrometers at the thickest point and 1 micrometer
or less in the center.
The average volume of the red blood cell is 90 to 95
cubic micrometers.
The shapes of red blood cells can change remarkably
as the cells squeeze through capillaries.
23. Concentration of Red Blood Cells in the Blood.
In normal men, per cubic millimeter is 5,200,000
(±300,000)
in normal women 4,700,000 (±300,000).
Persons living at high altitudes have greater numbers of
red blood cells.
Quantity of Hemoglobin in the Cells.
Red blood cells have the ability to concentrate hemoglobin
in the cell fluid up to about 34 grams in each 100
milliliters of cells.
24. In men :15 grams of hemoglobin per 100 milliliters of
cells
In women: 14 grams per 100 milliliters.
each gram of pure hemoglobin can combine 1.34
milliliters of oxygen.
In normal man, 20 milliliters of oxygen can be carried
in combination with hemoglobin in each 100
milliliters of blood.
in normal woman, 19 milliliters of oxygen can be
carried.
25.
26. .each of the four iron atoms can combine reversibly
with one molecule of O2
Each hemoglobin molecule can pick up 4 O2
passengers in the lungs.
98.5% of the O2 is carried in the blood is bound to
hemoglobin
Due to iron, hemoglobin is a pigment
O2 binds loosely to iron atoms so that the
combination is easily reversible
27. Each hemoglobin molecule contain 4
hemoglobin chains :Alpha , beta, gama ,
delta chains.
In adults: hemoglobin A ; 2 alpha and 2 beta
chains
Sickle cell anemia results from abnormalities
in 2 beta chains of hemoglobin
28. Transport and storage of iron
Iron in plasma : transferrin
Iron inside cell cytoplasm: ferritin (storage
iron)
Small quantities as insolube hemosederin
29. Transferrin delivers iron to erythroblast cells
in bone marrow to form hemoglobin
Low transferrin in blood failure to
transport iron to the erythroblasts severe
hypochromic anemia
Hypochromic anemia: red cells that contain
much less hemoglobin than normal
30. When red blood cells are destroyed, the
hemoglobin released from the cells is
ingested by monocyte-macrophage cells.
There, iron is liberated and is stored mainly
in the ferritin pool to be used as needed for
the formation of new hemoglobin.
31. Life span and destruction of RBC’s
circulate for 120 days before being destroyed
do not have a nucleus ,mitochondria, or
endoplasmic reticulum
they do have cytoplasmic enzymes that are
capable of metabolizing glucose and forming
small amounts of ATP.
32. Life span and destruction of RBC’S
Red cells are destructed in the spleen
the hemoglobin is phagocytized by
macrophages:
especially by the Kupffer cells (liver)
macrophages of the spleen and bone marrow.
Iron and bilirubin are released into the blood
33. deficiency of hemoglobin in the blood ,
which can be caused by too few RBC’s
1. Blood Loss Anemia.
2. Microcytic Hypochromic Anemia
3. Aplastic Anemia.
4. Megaloblastic anemia.
34. 5. Hemolytic anemia (hereditary)
hereditary spherocytosis
sickle cell anemia
West African and American blacks,
sickle cell disease “crisis”
35.
36. erythroblastosis fetalis
Rh-positive red blood cells in the fetus are
attacked by antibodies from an Rh-negative
mother
effects of anemia:
1. greatly increased cardiac output
2. increased pumping workload on the heart.
37. 1. Secondary polycythemia
causes:
too little oxygen in the breathed air (high
altitudes)
failure of oxygen delivery to the tissues ( in
cardiac failure) ex: Physiologic
polycythemia
38. 2. Polycythemia vera ( erythremia)
Genetic
The blast cells no longer stop producing red
cells when too many cells are already present
Hematocrit & total blood volume increase
Cyanotic (bluish )skin
39.
40. The mobile units of the body’s protective
system
Formed in:
Bone Marrow
lymph tissue
After formation, they are transported in the
blood to different parts of the body where
they are needed.
43. Granulocytes & monocytes protect the body
by phagocytosis
The lymphocytes and plasma cells function
mainly in connection with the immune
system.
44. Concentrations of the Different White Blood
Cells in the Blood.
adult human being has about 7000 white
blood cells per microliter of blood
The normal percentages of different WBC’s
45. granulocytes:
normally 4 to 8 hours circulating in the blood
and another 4 to 5 days in tissues
In times of serious tissue infection,this total
life span is often shortened to only a few
hours because the granulocytes are
destroyed.
46. The monocytes
10 to20 hours in the blood
Then ,through the capillary membranes into the
tissues.
Once in the tissues , they become tissue
macrophages
tissue macrophages can live for months unless
destroyed while performing phagocytic functions.
47. Lymphocytes
life spans of weeks or months
enter the circulatory system continually ,from the
lymph nodes and other lymphoid tissue.
After a few hours, they pass out of the blood
back into the tissues by diapedesis.
Later, they re-enter the lymph and return to the
blood again and again
48. It is mainly the neutrophils and tissue
macrophages that attack and destroy
invading microorganisms
The neutrophils
mature cells
attack and destroy bacteria even in the
circulating blood.
49. Monocyte-tissue macrophages
Monocytes
immature cells while still in the blood and have little ability to
fight infectious agents at that time.
tissue macrophages
begin life as blood monocytes
They enter the tissues
They swell to a size that can barely be seen with the naked eye.
extremely capable of combating intratissue disease agents
50.
51. Neutrophils and monocytes can squeeze
through the pores of the blood capillaries by
diapedesis
Both neutrophils and macrophages can move
through the tissues by ameboid motion,
Chemotaxis:chemical substances in the
tissues cause both neutrophils and
macrophages to move toward the source of
the chemical .
52. neutrophils and macrophages main function
is phagocytosis
1. Antibodies adhere to bacterial membrane to
make it susceptible to phagocytosis
2. the antibody combine with C3 . C3
molecules, in turn, attach to receptors on
the phagocyte membrane.
This selection and phagocytosis processis
called opsonization.
53.
54. single neutrophil can usually phagocytize 3 to
20 bacteria
neutrophils are not capable of phagocytizing
particles much larger than bacteria
55. Macrophages
more powerful phagocytes than neutrophils
phagocytizing as many as 100 bacteria.
They also have the ability to engulf much
larger particles (red blood cells ,malarial
parasites)
56.
57. The phagocytic vesicle fuse with lysosomes and
other granules and create digestive vesicle
Neutrophils and macrophages:
1. proteolytic enzymes
2. lipases
3. oxidizing agents
58. Composed of :
Monocytes
mobile macrophages
fixed macrophages
59. Tissue Macrophages:
the Skin and Subcutaneous Tissues (Histiocytes)
Macrophages in the Lymph Nodes
Alveolar macrophages in the lungs
Kupffer cells in the liver
Macrophages of the Spleen and Bone Marrow
Microglia in the brain
60. Defense lines
a First Line of Defense :
Tissue Macrophage.Within minutes begin their phagocytic
actions
Second Line of Defense :
Neutrophil Invasion of the Inflamed Area Is a within a few
hours
Neutrophilia: acute increase in the number of neutrophis
the number of neutrophils in the blood sometimes increases
from a normal of (4000 to 5000) 15,000 to 25,000 )neutrophils
per microliter
61. Defense lines
Third Line of Defense : Second Macrophage Invasion into
the Inflamed Tissue.
Fourth Line of Defense : Increased Production of
Granulocytes and Monocytes by the Bone Marrow Is
It takes 3-4 days for the new granulocytes & monocytes to
leave the bone marrow
62. Pus: cavity is often excavated in the inflamed
tissues that contains varying portions of necrotic
tissue, dead neutrophils, dead macrophages, and
tissue fluid
63. 2% of all the blood leukocytes
weak phagocytes,
parasitic infections
.
64.
65. release substances as:
1. hydrolytic enzymes
2. highly reactive forms of oxygen
3. major basic protein
66. In allergic reactions:
1. detoxify some of the inflammation-
inducing substances released by the mast
cells and basophils and probably
2. phagocytize and destroy allergen-antibody
complexes
thus preventing excess spread of the local
inflammatory process.
67. Basophils In the blood
basophils are similar to tissue mast cells
mast cells and basophils release:
1. heparin
2. Histamine
3. bradykinin
68. They play an important role allergic reactions
69.
70. Release of
1. histamine,
2. bradykinin,
3. serotonin,
4. heparin,
5. slow-reacting substance of anaphylaxis
6. lysosomal enzymes
71. Low WBC’s production
Without treatment, death often ensues in less
than a week after acute total leukopenia
begins.
72. Causes of aplasia of the bone marrow
Irradiation of the body by x-rays or gamma
rays
drugs and chemicals that contain benzene
chloramphenicol (an antibiotic), thiouracil
(used to treat thyrotoxicosis), and even
various barbiturate hypnotics, on very rare
occasions cause leukopenia
73. Uncontrolled production of white blood cells
can be caused by cancerous mutation of
1. myelogenous cells
2. lymphogenous cells.
74. Blood cells that are concerned with acquired
immunity
Present in lymph nodes and other lymphoid
tissues
Acquired immunity: the formation of antibody
and/or activation of lymphocytes that attack
and destroy the specific invading organism or
toxin.
75. Types of Acquired Immunity:
1. Humoral (B-cell ) immunity: B lymphocytes
produce antibodies.
2. Cell mediated (T-cell) immunity: formation
of activated T-lymphocyte that are
specifically crafted in L.N to destroy the
foreign agent
76. Both types are initiated by antigen
Antigen: is a large molecule with a special
epitope ( protein /polysaccharide ) on its
surface to be recognized
It starts When the invading antigen reaches
the lymphoid tissue (lymph nodes, spleen,
thymus …)
77.
78.
79. derived originally in the embryo from pluripotent
hematopoietic stem cells
Lymphocytes that migrate and differentiate in the
thymus form T-lymphocyte
Lymphocytes that differentiate in the fetal liver
and bone marrow form B-lymhocytes
After differentiation , B,T lymphocytes migrate to
lymphoid tissues throughout the body
80. B-lymphocytes remain dormant in lymphoid tissue
Macrophages phagocytize the antigen and present it
to T& B-lymphocytes
T-helper cells activate B-lymphocytes
B-lymphocytes enlarge and differentiate to form
plasma cells
Mature plasma cells produce gamma gobulin
antibodies
Antibodies are secreted into the blood
81. IgM, IgG, IgA, IgD, and IgE.
Ig stands for immunoglobulin
75% of Ig’s of a normal person are IgG
IgE involved in allergy
82. T-lymphocytes types and function:
T-helper cells:
most numerous T-cells,
major regulator of all immune functions by forming
lymphokines (interleukins, interferon …)
in the abscense of T-helper cells the immune system is
paralyzed
83.
84. T-helper cells functions:
1. Stimulation of Growth and Proliferation of
Cytotoxic T Cells and Suppressor T Cells
2. Stimulation of B-Cell Growth and
Differentiation to Form Plasma Cells and
Antibodies.
3. Activation of the Macrophage System.
4. Feedback Stimulatory Effect on the Helper Cells
Themselves.
85.
86.
87. T-lymphocytes types and functions:
Cytotoxic T Cells(killer cells):
has a protien receptor that bind to a specific
antegin and secret perforins that punchholes
in the attacked antigen and release cytotoxic
substances
after that they pull away and kill more cells
88. Cytotoxic T-cells
They are lethal to cells invaded by viruses ,
cancer cells , and any other foreign cells
89.
90.
91. T-lymphocytes types and functions:
Supressor T-cells :
Capable of suppressing the functions of both
cytotoxic and helper T cells
plays an important role in limiting the ability of
the immune system to attack a person’s own
body tissues, called immune tolerance
Failure of the Tolerance Mechanism Causes
Autoimmune Diseases.
92. Old people
after destruction of the body’s own tissues ,
releasing considerable quantities of “self-
antigens” that cause acquired immunity
• Rheumatoid fever
• Glomerulonephritis
• myasthenia gravis
• lupus erythematosus,
93. Other functions:
Delayed-reaction allergy is caused by
activated T cells and not by antibodies
on repeated exposure, it does cause the
formation of activated helper and cytotoxic T
cells
the eventual result of some delayed-reaction
allergies can be serious tissue damage in the
tissue area where the instigating antigen is
present.
94. “Allergic” Person,
Excess IgE Antibodies
Genetically passed
IgE has strong propensity to attach to mast
cells and basophils. ,results in immediate
change of the membrane and rupture of
these cells and releasing substances that
causes an allergic reaction (anaphylaxis, hay
fever,asthma…)
95.
96. Thrombocytes
(1-4 micrometer in diameter)
fragments of another type of
cell found in the bone marrow,
the megakaryocyte.
Function : activate the blood
clotting mechanism
Normally: 150,000 -300,000
cells per microliter of blood.
97. Lack nuclei , cannot reproduce
They have contractile proteins in their cytoplasm:
1. actin
2. Myocin
3. Thrombosthenin
Residual E.R & G.A that synthesize enzymes and store
Ca⁺²
Able to form ATP ,ADP , Fibrin stabilizing factor
Glycoprotiens on its cell membrane
98. replaced once every 10 days
Half life 8-12 days
Removed mainly by spleen macrophages
in other words, about 30,000 platelets are
formed each day for each microliter of blood.
99.
100. Means prevention of blood loss
After a vessel is ruptured, achieved by:
1. Vascular constriction
2. Platelet plug
3. Blood clot formation
4. Growth of fibrous tissue into the clot to
close the hole permanently
101. Vascular constriction
Trauma to the blood vessel will cause its smooth
muscles to contract ,to reduce blood flow from it
for the smaller vessels, platelets release a
vasoconstrictor substance, thromboxane A2
The more severe a trauma is , the greater the
degree of vascular spasm
Last from minutes to hours
102.
103. Platelet plug.
When platelets comes to contact with
exposed collagen
1. change in shape and contract
2. They become sticky and adhere to collagen
and von willbrand factor
3. They secrete ADP & thromboxane A2 that
activate other platelets and attract them
104. Blood coagulation
form in:
15-20 minutes in sever trauma
1-2 minutes in minor trauma
Activator substances & blood proteins adhere and
initiate clotting process
Within 3 minute a clot it formed
after 20 minute the clot retracts to close the vessel
even further
105.
106. Fibrous organisation or dissolution of the
blood clot
The clot is either invaded by fibroblasts which
forms C.T through the clot. or it can dissolve
107. Mechanism of blood coagulation.
a complex cascade of chemical reactions occurs in
the blood involving Coagulation factors. the net result
is the formation of prothrombin activator.
The prothrombin activator catalyzes conversion of
prothrombin into thrombin.
the thrombin acts as an enzyme to convert
fibrinogen into fibrin fibers that enmesh platelets,
blood cells, and plasma to form the clot.
108.
109. Prothrombin is a plasma protein formed in
the liver
Vitamin K is required in the liver for the
formation of prothrombin and other clotting
factors
Lack of vitamin K or presence of liver
diseases lead to bleeding tendency
110.
111. Conversion of prothrombin to thrombin
Prothrombin activator , In the presence of
Ca⁺² causes the conversion of prothrombin to
thrombin.
Platelets also help in prothrombin conversion
Thrombin polymerizes fibrinogen into fibrin
within 10-15 seconds
112. Conversion of fibrinogen to fibrin-clot
formation
Fibrin stabilizing factor produced by platelets
add strength to this fibrin meshwork
Blood clot meshwork of fibrin fibers running in
all directions & entrapping blood cells ,platelets
& plasma
113. Clot retraction-serum
few minutes after clot is formed , it contracts,
expressing the fluid from it( serum )
serum lacks fibrinogen and clotting factors
Serum differs from plasma that it lacks these
clotting factors and so it cannot clot
114. platelet thrombosthenin , actin, and myosin
molecules causes clot contraction
The contraction is activated and accelerated
by thrombin & calcium ions
the clot retracts
115. Initiation of Coagulation: Formation of
Prothrombin Activator
1. extrinsic pathway that begins with trauma to
the vascular wall and surrounding tissues.
2. intrinsic pathway that begins in the blood
itself.
Blood clotting factors play major roles
116.
117.
118. Extrinsic pathway
Traumatized vascular wall that comes in contact
with blood results in release of tissue
factor(tissue thromboplastin) that function as a
proteolytic enzyme
Activation of factor X
Xa combine with tissue factor and factor V in the
presence of Ca⁺² to form prothrombin activator
Prothrombin is then convertedto thrombin &
clotting proceeds
Factor V in the activator complex is inactive until
thrombin is formed,the proteolytic action of
thrombin activate factor V
119. Activated Factor X is the actual protease that
causes splitting of prothrombin to form
thrombin
Factor V is an accelerator
120. Intrinsic pathway
begins with trauma to the blood itself or
exposure of the blood to collagen from a
traumatized blood vessel wall.
121.
122. Intrinsic pathway
Blood trauma activate factor XII
XIIa activate factor XI
XIa activate factor IX
XIa along with VIII and platelet phospholipds
activate factor X
Missing factor VIIIhemophilia
Lack of plateletsthrombocytopenia
Xa with factor V prothrombin activator
123. Ca⁺² is an accelerator
in their absence blood clotting in either pathways
does not occur
Both pathways occur simultaneously:
Clotting needs 15seconds in extrinsic pathway
Clotting needs 1-6 minutes in intrinsic pathway
124. Prevention of Blood Clotting in the Normal
Vascular System
Endothelial surface factors:
Smoothness of endothelial surface
Glycocalyx layer on endothelium/repels
clotting factors
Thrombomodulin: bind thrombin
Anticoagulants in blood :antithrombin III,
heparin
125. Lysis of clot
Plasmin
It destroys many of the clotting factors
Plasminogen entrapped inside the clot
t-PA (tissue plasminogen activator) is slowly released
from injured tissue few days after the bleeding stops
Entrapped plasminogen is activated into plasmin
126. 1. Vitamin K deficiency
2. Hemophilia
3. thrombocytopenia
127. Vitamin K deficiency
Vitamin K is necessary for liver formation of five of
the important clotting factors:
1. prothrombin
2. Factor VII
3. Factor IX
4. Factor X
5. protein C
In the absence of vitamin K, subsequent
insufficiency of these coagulation Factors in the
blood can lead to serious bleeding tendencies.
128. Hemophilia
In males
85% factor VIII deficiency :hemophilia A
(classic hemophilia)
15% factor IX deficiency
Both factors are transmitted genetically
129. Hemophilia
Bleeding occur following trauma
Even mild trauma can cause bleeding for days (e.x:
tooth extraction)
Treatment of classic hemophilia is factor VIII
injection
Hemophilia bleeding from large vessels
130. Von Willbrand disease (vWD)
The most common hereditary coagulation
abnormality
Defeciency of Von Willbrand factor (vWF)
vWF: protien required for platelet adhesion
131. Thrombocytopenia
Low number of platelets circulating in the blood
Bleeding from small capillaries
Multiple small purplish blotches
thrombocytopenic purura
132. Thrombocytopenia
Bleeding occur when platelet number falls below
50,000/microliter
Levels below 10,000/microliter are lethal
Idiopathic thrombocytopenia:
specific antibodies destroy platelets
Treatment of thrombocytopenia:
A. fresh whole blood transfusion
B. splenectomy
133. Thromboembolisms
Thrombus: abnormal clot that develop in a bood vessel
Emboli: free flowing clot
Causes:
Roughened endothelial surface
Slowly flowing blood
Treatment : genetically treated t-PA delivered through a
catheter
135. Disseminated intravascular coagulation.
the clotting mechanism becomes activated in widespread areas of the
circulation
Occurs in widespread septicemia in which endotoxins activate clotting
mechanisms
Clots are small but numerous
Plug small peripheral blood vessels
Diminishes oxygen and nutrients delivery
leads to circulatory shock an death in 85% of patients
May cause bleeding
136. Anticoagulants
1. Heparins
increases clotting time to 30 minutes (normal=6
minutes)
the change in clotting time occurs immediately
action remains 1.5-4 hours
heparin is destroyed by the enzyme heparinase
137. Anticoagulants
2. Coumarins
Ex:warfarin
blocking the action of vitamin K
Coagulation is not blocked immediately
Normal coagulation returns after 1-3 days of
discontinuing coumarin therapy
INR international normalised ratio
141. Prothrombin time
Indicate the
concentration of
prothrombin in the
blood
Normal P.T is 12
seconds
Hinweis der Redaktion
centrifuging blood in a “hematocrit tube” until the cells become tightly packed in the bottom of the tube
In severe anemia= 0.10, a value that is barely sufficient to sustain life.
Polycythemia:excessive production of RBC’s
a substance must be used that does not readily penetrate capillary membranes but remains in the vascular system after injection.
Evans blue dye binds to the plasma protien
Blood volume can be calculated if one knows the hematocrit (the fraction of the total blood volume composed of cells),
Blood contains both extracellular fluid (the fluid in plasma) and intracellular fluid (the fluid in the red blood cells)
The blood volume is especially important in the control of cardiovascular dynamics.
solutes in the extracellular fluid (the plasma +intestitial fluid).
Plasma protiens :the most plentiful
Angiotnsin:regulate salt balance
1-Plasma protiens carry out many of the functions of plasma
Because they are the largest of plasma constituants and dispearsed as colloid
they dont exit through pores in the capillary wall, so their presence in plasma and absence in interstitial fluid establish an osmotic gradient between blood and interstital fluid.this prevent excessive loss of plasma from capillaries into the interstetitial fluid, thus
Carbonic anhydraze:enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water to form carbonic acid (H2CO3), increasing the rate of this reaction several thousandfold.
The rapidity of this reaction makes it possible for the water of the blood to transport enormous quantities of CO2 in the form of bicarbonate ion (HCO3–) from the tissues to the lungs, where it is reconverted to CO2 and expelled into the atmosphere as a body waste product
Acid base buffer: RBC’s are responsible for most of the acid base buffering of whole blood
A hemoglobin molecule has two parts
the globin portion : a protien made up of polypeptide chains.
four iron containing, nonprotien groups known as heme groups. each of which is bound to one of the polypeptides.
O2 is poorly soluble in the plasma
it appearse reddish when combined with O2 and bluish when deoxygenated
Oxygen carried in the molecular form
When iron quantities in plasma falls low ferritin is removed and transported in the form of transferrin
1.After rapid hemorrhage
2.In chronic blood loss
3. Bone marrow aplasia :means lack of functioning bone marrow. ex: after excessive x-ray treatment
4. Loss of vitamin B12 or folic acid leads to slow reproduction of erythroblasts, as a result red cells grow to large with odd shapes , these cells rupture easily
5. hereditary spherocytosis, the red cells are very small and spherical rather than being biconcave discs. On passing through the splenic pulp and some other tight vascular beds, they are easily ruptured by even slight compression.
Crisis: circle of events called a sickle cell disease “crisis,” in which low oxygen tension in the tissues causes sickling, which leads to ruptured red cells, which causes a further decrease in oxygen tension and still more sickling and red cell destruction Once the process starts, it progresses rapidly, eventuating in a serious decrease in red blood cells within a few hours and, often, death.
hemoglobin Scontaining faulty beta chains in the hemoglobin molecule,
Sickle appearance
Capillaries blocked by viscous blood
Increased arterial pressure
Bone Marrow (granulocytes and monocytes and a few lymphocytes
lymph tissue (lymphocytes and plasma cells)
various lymphogenous tissues—especially the lymph glands, spleen, thymus,tonsils, and various pockets of lymphoid tissue elsewhere in the body, such as in the bone marrow and in so-called Peyer’s patches underneath the epithelium in the gut wall
EOSINOPHILS:red dye eosin
BSOPHILS: BASIC BLUE DYE
NEUTROPHILS neutral no dye preference
7000 in comparison with 5 million rbc’s
Neutrophils 62 %
Lymphocytes 30%
Eosiophils, badophils,monocytes
Once in the tissues, they swell to much larger sizes to become tissue macrophages, and, in this form, can live for months unless destroyed while performing phagocytic functions.
Lymphoid tissuebloodby diapedisisto tissues, and so on
Neutrophils and monocytes can squeeze through the pores of the blood capillaries by diapedesis
Both neutrophils and macrophages can move through the tissues by ameboid motion,
Chemotaxis: chemical substances in the tissues cause both neutrophils and macrophages to move toward the source of the chemical
C3 (product of the complement cascade).
Neutrophils projects pseudopodia around the particle
Pseudopodia enclose the particle
Phagocytic vesicle (phagosome) is formed inside the neutrophil
macrophages can extrude the residual products and often survive and function for many more months.
proteolytic enzymes to digest bacteria
lipases(only in machrophages) that digest thick lipid membrane possessed by some bacteria , ex: tuberculosis bacillus
oxidizing agents to kill bacteria
Fixed macrophages :large portion of monocytes becomes attached to the tissues and remains attached for months or even years until they are called on to perform specific local protective functions
In the lymph nodes: if the particles are not destroyed locally in the tissues, they enter the lymph and flow to the lymph nodes
The foreign particles are then trapped in these nodes in a meshwork of sinuses lined by tissue macrophages
In the lung: If the particle is not digestible, the macrophages often form a “giant cell” capsule.
Ex: around tuberculosis bacilli, silica dust particles, and even carbon particles
Kupffer cells: bacteria that enteR Through the GIT
SPLEEN AND BONE MARROW: If the organism succeed in entering the blood
Spleen:This peculiar passage of blood through the cords of the red pulp provides an exceptional means of phagocytizing unwanted debris the blood, including especially old and abnormal red blood cells.
parasites are too large to be phagocytized
eosinophils attach themselves to the parasites by way of special surface molecules and release substances that kill many of the parasites
masT CELLS:located immediately outside many of the capillaries in the body.
HEPARIN:preveents blood coagULATION
IgE) can attach to mast cells and basophils.
The attachment of antigen to antibody causes the mast cell or basophil to rupture and release ….
Normally, the human body lives in symbiosis with many bacteria, Any decrease in the number of white blood cells immediately allows invasion of adjacent tissues by bacteria that are already present
Bone marrow aplasia : means lack of functioning bone marrow.
Lymphocytic lukemia: cancerous production of lymphoid cells
Myelogenous leukemia : begins by cancerous production of young myelogenous cells in the bone marrow and then spreads throughout the body
derived originally in the embryo from pluripotent hematopoietic stem cells
Lymphocytes that migrate and differentiate in the thymus form T-lymphocyte
Lymphocytes that differentiate in the fetal liver and bone marrow form B-lymhocytes
After differentiation , B,T lymphocytes migrate to lymphoid tissues throughout the body
Gray: HIV
T-helper cells are the inactivated cells in (AIDS)
Cytotoxic T Cells(killer cells):has a protien receptor that bind to a specific antigen and secret perforins that punch holes in the attacked antigen and release cytotoxic substances
preventing the cytotoxic cells from causing excessive immune reactions that might be damaging to the body’s own tissue
Rheumatoid fever:in which the body becomes immunized against tissues in the joints and heart, especially the heart valves, after exposure to a specific type of streptococcal toxin that has an epitope in its molecular structure similar to the structure of some of the body’s own self-antigens
Glycoprotiens on its cell membrane that repulses adherence to normal endothelium & causes adherence to injured endothelial cells and exposed collagen
When platelets comes to contact with exposed collagen
change in shape and contract
They become sticky and adhere to collagen and von willbrand factor
They secrete ADP & thromboxane A2 that activate other platelets and attract them
small vascular holes do develop throughout the body each day—the cut is often sealed by a platelet plug, rather than by a blood clot
VON WILLBRAND LEAKS FROM PLASMA
the thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that enmesh platelets, blood cells, and plasma to form the clot.
Prothrombin activator , In the presence of Ca⁺² causes the conversion of prothrombin to thrombin.
Platelets also help in prothrombin conversion
Fibrin stabilizing factor produced by platelets add strength to this fibrin meshwork
3. As The clot retracts the edges of the broken blood vessel are pulled together, thus contributing still further to the ultimate state of hemostasis.
Blood clotting factors play a major role:. Most of these are inactive forms of proteolytic enzymes.When converted to the active forms, their enzymatic actions cause the successive cascading reactions of the clotting process
-Traumatized vascular wall that comes in contact with blood results in release of tissue factor(tissue thromboplastin) that function as a proteolytic enzyme
-Activation of factor X
-Xa combine with tissue factor and factor V in the presence of Ca ions to form prothrombin activator
Prothrombin is then converted to thrombin & clotting proceeds
Factor V in the activator complex is inactive until thrombin is formed,the proteolytic action of thrombin activate factor V
Blood trauma activate factor 12
XIIa activate factor 11
XIa activate factor 9
XIa along with VIII and platelet phospholipds activate factor X
Xa with factor V prothrombin activator
****
****factor VIII has 2 active components:
Smallncomponentits loss lead toclassic hemophilia
Large componentits loss lead to von willbrand disease
Roughened endothelial surface of vessel (arteriosclerosis,infection, trauma)
*Immobility of patients in bed causes intravascular clotting because of blood stasis in one or more of the leg veins
*The clot grows in size and disengage from attachment & flows freely in blood & cause massive blockage in pulmonary artery
If blockage in one pulmonary artery, death may occur after several hours to days
If it is large enough to block both pulmonary arteries, immediate death ensues
Vitamin k blockage:Depresses the liver formation of Prothrombin & factors VII,IX,X