Connective tissue in general and blood in detail along with applied clinical anatomy.

1. CONNECTIVE
TISSUE
• GENERAL
• BLOOD
By - Dr. Bhavika Nagpal
PG Prosthodontics 1st year

2. Contents :
• Introduction
• Classification
• Components
• Functions
• Blood
• Applied anatomy
• Conclusion

3. Introduction
What is Connective tissue ?
• Connective tissue is the term applied to a tissue – that
fills the interstices between more specialized elements;
and serves to hold them together and support them. That
is why it is also k/a Support tissue .
• The connective tissue is the most abundant and
widespread tissue in the body.

4. Lets take an idea of what CT is……
1. When we section a salivary gland epithelium lined acini
and duct are seen under microscope.
Filling the interstices between these elements is a
connective tissue, forming its stroma.
It provides support to delicate epithelial cells.
Secretory elements are held together by CT (mainly
reticular fibers).

6. 2. During dissection when skin is lifted off from underlying
tissues, two are seen to be united by a delicate network of
fibers.
This network is superficial fascia, which is an example of
connective tissue.

8. 3. An epithelium lined mucosa is separated by short
distance from thick layer of muscles.
This interval b/w mucosa and muscle is filled by connective
tissue, which constitutes submucosa.
This CT holds the various layers in the wall of hollow
organs together.

10. Classification of
Connective tissue

11. Classification
Connective tissue
Connective tissue
proper
Specialized connective
tissue

12. Connective tissue proper
Dense
(less ground substance, more
collagen fibers)
Regular
- Tendons, ligaments
Irregular
- Submucosa, fascia
Loose
(more ground substance, less
collagen fibers)

13. Specialized Connective Tissue :
Reticular Adipose Bone
Cartilage Blood

14. Components of
Connective tissue

15. Components
Fibers
Ground
substance
Cells

16. 1. Fiber

17. Fibers
Type Purpose Components Location
Collagen
fibers
Bind bones and other
tissues to each other
Alpha polypeptide
chains
tendon, ligament, skin,
cornea, cartilage, bone,
blood vessels, gut, and
intervertebral disc.
Elastic
fibers
Allow organs like
arteries and lungs to
recoil
Elastic microfibril and
elastin
extracellular matrix
Reticular
fibers
Form a scaffolding for
other cells
Type III collagen liver, bone marrow, and
lymphatic organs

20.  Collagen fibers

21. Collagen fibers
Physical nature :
• Appear white with naked eye.
• Resist considerable tensile forces (stretching) without increase in length.
• Also they are pliable, can bend easily.
• Run in bundles.
• Show periodic striations
• Becomes soft – when treated with weak acid or alkali.
• Destroyed – when treated with strong acids.
• Gelatine form – when boiled.

22. Chemical nature :
• They are named so because it is mainly made of protein
called collagen.
Production of collagen :

23. Long chain of amino acids like
glycine(C),hydroxyproline(V),
hydroxylysine(V) are linked in cell
Polypeptide chain is
formed
3 such chains are arranged to form
1 Pro-Collagen molecule
They leave the cell forming
Tropo-collagen molecule
Microfibrils (3.5 nm in D)
Fibrils (20-200nm in D)
Collagen fiber
Important mediators of
collagen production
1. Amino acids &
2. rough Endoplasmic reticulum
3. Fibroblast
4. Vit C
5. Oxygen

25. Tissue Type of collagen
1. Alveolar bone Type I (mainly)
Type III (immature or healing )
2. PDL Type I (80%)
Type III (20%)
3. Cementum Type I (mainly)
Type III (Early stages of cementogenesis)
4. Pulp, Dentin,Gingiva Type I (mainly)
Type III
5. Basal Lamina Type IV
Type VII
6. Stroma of Connective
tissue
Upper stroma (lamina propria) – Type III , IV
Deeper stroma – Type I

26. Uses of collagen
 Skinfillers
 Woundhealing – asit promote healing.
 In wounds like – chronic nonhealing,
• -- necrotic,
• -- burns,
• -- sites of donatedtissue,
• -- skingrafts.
 GTR– collagen basedmembranes for periodontal & implanttherapy
• -- in Oral surgery, asbarriers toprevent fast growing cells of gingival epithelium
 Vascularprosthetics–for peripheral nerve regeneration & vascularprostheses.
 Skinrevitalization
 TreatmentofOsteoarthritis.

27. Collagen defects
• Mutations that affect type I collagencause osteogenesis imperfecta.Thisgives
weakbones that fractureeasily.
• Mutations thataffect type II collagen causechondrodysplasias, in which the cartilage
is abnormal andthis leadsto bone andjoint deformities.
• Mutations that affect type III collagencauseEhlers- Danlos sydrome,which leadsto
fragile skin,blood vesselsandhypermobile joints.
• In Marfan's syndrome,there aremutations in the fibrillin gene,which affects
tissuesrich in elastic fibres, suchasthe wall of the aorta. Thismeans that the
aorta ismoreprone to rupture.

28.  Reticular Fibers

29. Reticular fibers
• Type III collagen fibers
• Show periodic striations.
• Differ from typical type I as they :
Much finer
Uneven in thickness
Form a network (reticulum) by branching i.e. they don’t run in bundles
More carbohydrates
Argentophil fibers – affinity for silver salts
Silver impregnation – stains Black
(vs collagen stains Brown)

30. • Location :
o Dental pulp
o Lymph nodes
o Bone marrow
o Basement membranes*
o Liver, spleen, kidneys
o Smooth muscles
o Nerve fibers

32.  Elastic Fibers

33. Elastic Fibers
Physical nature : They can be stretched like a rubber band and return to
original length when tension is released so named as Elastic fibers.
• Run singly or in branches (not in bundles)
• Periodic striations are not present, unlike collagen fibers.
• Unlike collagen, they are not effected by acids, alkalies or boiling.
• Digested by enzyme - Elastase

34. Chemical nature :
• Main protein – Elastin – forms amorphous core
• Elastin formed by smaller units- Tropoelastin
• Amino acids – Valine, Alanine, Desmosine*
• Desmosine – AA exclusively found in elastic tissue
• Outer fibril composed of glycoprotein Fibrillin

37. 2. Cells

38. CELLS
Connective
tissue cells
Intrinsic
component
cells
Immune cells

39. Intrinsic component cells
Fibroblast Undifferentiated
mesenchymal cells
Pigment cells Fat cells
Immune cells
Lymphocytes
& Plasma
cells
Monocytes Mast cells
Neutrophils &
eosinophils
(rare)

41. • Intrinsic component of cells

42.  Fibroblast

43. Fibroblast
Most numerous cells of CT – Spindle shaped, fixed cells.
Named so because help in production of Collagen fibers.
Also produce reticular and elastic fibers.
(when associated with reticular fibers k/a reticular cells)
Inactive form – Fibrocytes
(Scanty cytoplasm; few organelles)
Active form – Fibroblast
• (Abundant cytoplasm; prominent nucleoli; ER, golgi complex,
mitochondria more conspicuous)
• Become active – when collage is needed. Eg- Wound repair

44.  Mature Fibroblasts are Specialized cells ; cannot convert themselves
to other cell types.

45.  Myofibroblasts- When cells resembling fibroblasts
contain actin and myosin and are present in association
with smooth muscles, with contractile function are k/a
Myofibroblast.
Help in retraction and shrinkage of scar.

47.  Undifferentiated mesenchymal cells

48. Undifferentiated mesenchymal cells
• Embryonic CT is k/a
mesenchyme.
• Made up of small cells
with slender branching.
• Various elements of
mature CT are derived
from them.
• Persist as such and these
are the cells from which
other types of cells are
formed when required,
unlike fibroblast.

49. ARE MESENCHYMAL STEM CELLS
(MSCS) TRUE STEM CELLS?
MSCs have great potential and clinical significance for tissue
engineering. They are adult multipotent cells capable of
differentiating to different types of tissues.
• MSCs are commonly known as “multi-lineage cells” because of
their wide range of potential applications.
• They are known to regenerate structure and connective tissues, repair
bones and cartilage
• Stimulate angiogenesis (after heart attacks)
• Reduce inflammation and scarring through their immunomodulatory
properties.
• They can also be found in adipose tissue, amnion, synovial fluids,
muscles, dermis, deciduous teeth, and umbilical cord tissue.

50.  Pigment cells

51. Pigment cells
Easily distinguishable because of brown pigment in their cytoplasm.
Many cells contain the pigment
• Those which actually synthesize melanin - Melanocytes
• Those that engulfed pigment released by melanocytes -
Chromatophores or Melanophores
Pigment epithelial cells, skin, iris etc.
Function – Prevent light (specially UV light) from reaching other
cells ; Provide differences in skin color.
Clinical Significance – Depicts the areas of healing as a result of
post-inflammatory hyperpigmentation.

53.  Fat cells

54. Fat cells
Small amount of fat (lipids) may be present in cytoplasm of many
cells, including fibroblasts.
Some cells store fat in larger amounts and become distended.
These cells are k/a fat cells ; adipocytes ; lipocytes .
Aggregation of fat cells constitute – Adipose tissue.

56. Buccal pad of fat

57. • Immune cells

58.  Lymphocytes

59. Lymphoctes
Lymphocytes
B-lymphocytes
(Bone marrow – blood
stream)
T- lymphocytes
(Bone marrow –
Thymus – blood stream)

60. Can be seen in normal CT.
Specially numerous when tissue undergoes (chronic) inflammation.
Ability to recognize the substances that are foreign to host body i.e.
differentiate between self and non-self.
Thus create antibodies to destroy the invaders.

61.  Plasma cells

62. Plasma cells
• Mature B-lymphocytes that lose their ability to divide further, represent
Plasma cells.
• Can be seen in normal CT ; number increases during inflammation.
• Chromatin forms 4-5 lumps in periphery of nucleus – Cartwheel
appearance.
• Cytoplasm filled with rER, except near nucleus where well developed
golgi complex is present.
• Produce antibodies – that can discharge locally ; into the circulation ;
or stored within cell in form of inclusions k/a Russell’s bodies.

64.  Macrophage cells

65. Macrophage cells
• They are derived from monocytes.
• Macrophages of CT are k/a histiocytes or clasmatocytes.
• They phagocytose the unwanted material, usually organic (including
bacterial invaded tissue ; damaged tissue)
• They can phagocytose inorganic materials injected in body like India
ink.
• They collectively form mononuclear phagocytic system.
• Fixed macrophages resemble - fibroblast; Free macrophages -
rounded. With kidney shaped nucleus, numerous lysosomes.
• Fused macrophages – multinucleated giant cells.

67.  Mast cells

68. Mast cells
• Originated from basophils of blood.
• Also k/a mastocytes or histaminocytes.
• Release histamine, associated with production of allergic reactions.
• Surface of mast cells contain antibodies (IgE), react with the antigen,
rupture to discharge histamine – producing local reactions like
urticaria, anaphylaxis etc

69. 3. Ground Substance

70. GROUND SUBSTANCE
• Colorless, transparent and homogenous matrix.
• Fills the space between cells and fibers of the CT.
• It is viscous and acts as medium of transport and also as a
barrier to the penetration of the tissues by foreign particles.
• Hold large amount of water.
• Formed mainly by two classes of components:
• Glycosaminoglycans
• Structural glycoproteins (Adhesion proteins)
Retained water and proteoglycans together form gel – that
provides stiffness to CT.

71. • Glycosaminoglycan formed by =
Protein core + Large polysaccharides
• GAGs linked together to form proteoglycans.
• Glycosaminoglycans of human gingival epithelium and
connective tissue.
Include :
1. Hyaluronic acid (HA),
2. Heparan sulfate (HS),
3. Dermatan sulfate (DS) and
4. Chondroitin-4 sulfate (ChS-4).
Neither ChS-6 nor keratan sulfate (KS) was observed.

73. Functions of
Connective tissue

74. Functions of CT
 Provide a matrix that serves to connect and bindthecells and
organs
 Give mechanical support to the body
 Storage of fat and certain minerals like calcium inthe bones
 Exchange of metabolites between blood and tissues
 Significant role in the repair and healing ofwounds
 For protection againstinfection

75. BLOOD

76.  Blood is calledthe riverof life.
 Specialized connective tissue.
 Average 70 kg man has almost 5L of blood.
 Blood has 2 main components :
• Plasma
• Cellular elements –
RBC
WBC
Platelets

77. Functions of blood
• Respiration: transport of O2 and CO2.
• Transport: hormone, nutrients, metabolic waste.
• Excretion of metabolic wastes to the kidney, lungs and skin.
• Regulation of body temperature by distribution of
body heat.
• Defense against infections (WBCs, antibodies).
• Maintenance of acid-base balance.
• Nutrition: transport of absorbed food material.

78. Physical properties of blood
• Specific gravity:-Whole blood:1.055 -1.065 kg/m³
• Viscosity: 5-6 times that of water.
• Mass: 6-8% of the body weight.
• Blood volume:~ 8%of body weight.~ 86% (ml/kg
body weight).
5-6 Liters in adults, [Infants have a larger blood volume
in proportion to body weight than adults].
• Osmotic pressure: 7-8 atmosphere at body temperature

79. Color of blood
• Generally , blood is red in color due to a pigment
present in blood called haemoglobin.
• Arterial blood is scarlet red while venous blood is
purple red.
• pH of blood is 7.4

80. Composition of blood

81. Composition of blood
• Blood consists of several types of cells floating around in
a fluid called plasma.
1. The red blood cells (RBCs) contain haemoglobin, a
protein that binds oxygen. RBCs transport oxygen and
remove carbon dioxide from the tissues.
2. The white blood cells fight infection.
3. The platelets help the blood to clot.
4. The plasma contains salts and various kinds of
proteins .

83. Other constituents are -
• Plasma proteins –albumin , globulin and fibrinogen.
• Carbohydrates – glucose
• Non protein substances –creatin, creatinine, xanthine,
hypoxanthine, urea and uric acid.
• Enzymes and antibodies .
• Inorganic substances – K , M, Cl, I, Fe and phosphate.
• Gases –oxygen , carbondioxide.

84. Plasma

85. PLASMA
• 90% water
• contains nutrients, electrolytes, plasma proteins, respiratory gases,
hormones, waste products etc.

87. Function of plasma
• Help in coagulation of blood- fibrinogen
• Defense mechanism- gamma globulin
• Transport of hormones – albumin and globulin
• Maintain acid base balance in blood
• Provide viscosity to blood

89. Formed elements of blood

90. FORMED ELEMENTS OF BLOOD
WBC
Platelets
RBC

91. RBC

92. Red Blood Cells (Erythrocytes)

93. Plasma half life of RBCs = 120 +_4 days
Plasma half life of transfused RBCs = 42 days
Destroyed in – Spleen (graveyard of RBCs)
Red pigment – Haemoglobin
Mature RBC – lack nucleus

94. Erythropoiesis
In the early
fetus, erythropoiesis takes place in the
mesodermal cells of the yolk sac.
By the third or fourth
month, erythropoiesis moves to the
liver.
After seven
months, erythropoiesis occurs in the
bone marrow

95. Haemoglobin
• Iron-containing protein that binds strongly, but reversibly to oxygen.
• Each hemoglobin molecule has four oxygen binding sites .
• Each erythrocyte has 250 million hemoglobin molecules.
• Normal blood contains 12–18 g of hemoglobin per 100mL blood.

96. Structure of Hb has two main components
1. Heme
 Aporphyrin with an Fe in the center.
 Porphyrin rings are found throughout biological systems and serve many
different roles including photosynthesis in green plants, delivering O2 in
muscles (myoglobin) and transporting O2 in blood (hemoglobin).
2. Globin
 Globin is the protein (polypeptide) surrounding the heme.
 Nomenclature:
globin + heme(Fe2+) = hemoglobin
globin + heme(Fe3+) = methemoglobin
 The overall structure of haemoglobin consists of four chains -
two alfa and two beta chains

98. WBC

99. White blood cells (Leucocyte)
White blood corpuscles or leucocytes are mobile force or soldiers of
the body because they migrate to the site of injury and infection,and
fight with invading microbes.
They perform their action by –
1. Scavenging
2. Diapedesis (amoeboid movement)
3. Pus formation
4. Phagocytosis
5. Formation of antibodies
6. Confer immunity
The dead leucocytes along with destroyed tissue cells, dead and live microbes and
exuded plasma form the pus.

102. Functions of different WBCs
• 1.Monocytes. They have a longer lifespan than many white blood cells
and help to break down bacteria. chronic inflammation)
• 2.Lymphocytes: They create antibodies to defend against bacteria,
viruses, and other potentially harmful invaders. (chronic inflammation)

103. • 3.Neutrophils: They kill and digest bacteria and fungi. They are the most
numerous type of white blood cell and your first line of defense when
infection strikes. (acute inflammation)
• 4.Basophils: These small cells appear to sound an alarm when infectious
agents invade your blood. They secrete chemicals such as histamine, a
marker of allergic disease, that help control the body's immune response.
• 5.Eosinophils: They attack and kill parasites, destroy cancer cells, and help
with allergic responses.

104. Platelets

105. Platelets
• Platelets, also called thrombocytes, are a component of blood whose function
(along with the coagulation factors) is to react to bleeding from blood vessel injury
by clumping, thereby initiating a blood clot.
• Platelets have NO cell nucleus: they are fragments of cytoplasm that are derived from
the megakaryocytes of the bone marrow, and then enter the circulation.
• Circulating inactivated platelets are biconvex discoid (lens-shaped) structures,2–
3 µm in greatest diameter.
• Activated platelets have cell membrane projections covering their surface. Platelets
are found only in mammals, whereas in other animals (e.g. birds, amphibians)
thrombocytes circulate as intact mononuclear cells
• Half life 7-11 days.

107. Functions of platelets
1.platelets are responsible for wound healing
2.platelets attach to the exposed vessel
3.platelets change fibrinogen into fibrin
•this fibrin creates a mesh onto which red blood cells collect
and clot
•the clot stops more blood from leaving the body
4.prevents bacteria from entering the body.

108. Hemostasis
• Hemostasis or haemostasis is a process which causes bleeding to
stop, meaning to keep blood within a damaged blood vessel
(the opposite of hemostasis is hemorrhage)
• It is the first stage of wound healing. This involves coagulation, blood
changing from a liquid to a gel.

110. Coagulation
• Coagulation is clotting of blood.
• Injured tissues release tissue factor (TF) .
• Prothrombin activator converts prothrombin to thrombin (an enzyme) .
• Thrombin joins fibrinogen proteins into hair- like molecules of insoluble fibrin
• Fibrin forms a meshwork (the basis for a clot).
• Blood usually clots within 3 to 6 minutes .

111. Clotting factors

113. Extrinsic pathway
• It initiates upon the introduction of cells, particularly
crushed or injured tissue, blood coagulation is activated
and a fibrin clot is rapidly formed.
• The pathway of blood coagulation activated by tissue
factor, a protein extrinsic to blood, is known as the
extrinsic pathway or tissue factor pathway.

114. Intrinsic pathway
• It initiates when injury occurs directly to blood vessel.
• the proteins required for such clotting to take place are
part of the intrinsic pathway of blood coagulation.
• Each protein circulates in the blood in an active form.

115. Bleeding time (BT)
• Bleeding time is the interval between the moment when bleeding starts and
the moment when bleeding stops.
• Bleeding time is prolonged in purpuras, but normal in coagulation
disorders like haemophilia.
• Bleeding time is noted as in Duke’s method.
A standard filter paper should be used every 30 seconds to draw off it until
the blood completely stops.
• The normal BT values run in the range of 2-9 minutes. The risk of
bleeding increases with BT values more than 10 minutes Normal bleeding
time is to 4 minutes.

116. Duke’s method

117. Clotting time (CT)
• Clotting time is the interval between the moment when bleeding
starts and the moment when the fibrin thread is first seen.
• Normal range is 8 - 15 minutes.
• Vitamin K dependent factors are 2 , 7, 9 and 10, which help in
coagulation of blood.

118. Capillary tube method

119. Prothrombin time (PT)
• The prothrombin time (PT) test measures how well and
how long it takes your blood to clot.
• It normally takes about 25 to 30 seconds.
• It may take longer if you take blood thinners.
• PT indicates total quantity of prothrombin
present in blood.

120. Lysis of clot
• Lysis of blood clot inside the blood vessel – Fibrinolysis
• Plasma protein –euglobulin called plasminogen
(profibrinolysin) when activated become plasmin
(fibrinolysin)
• Plasmin digests fibrin fibers as well as coagulant factors I,II, V,
VIII and XII

121. Dry socket
• A dry socket is a condition that may result after a tooth
extraction if the blood clot that normally fills the socket is lost.
• The dry socket leaves underlying nerves exposed, which is very
painful.

122. Undesirable Clotting - :
• Thrombus - A clot in an unbroken blood vessel. Can be
deadly in areas like the heart .
• Embolus - A thrombus thatbreaks away and floats freely in
the bloodstream. Can later clog vessels in critical areas such as
the brain .

123. When an air bubble enters a vein, it's called venous air embolism.
When an air bubble enters an artery, it's called an arterial air embolism.
These air bubbles can travel to your brain, heart, or lungs and cause a
heart attack, stroke, or respiratory failure.
Air embolisms are rather rare and fatal.
Thus always remove air bubble from syringe before injecting

124. Blood transfusion
• The AB0 and Rhesus (Rh) systems - used for blood
transfusion.
• Antibodies that are specific at detecting a particular ABO
antigen are on RBCs.

126. Normal values
• RBC COUNT-
Men : 4- 5 millions / mm³
Women : 4.5million / mm³
Total number of red cells = 4 – 5 millions / mm³
• WBC COUNT -
Men and women - 4000 – 11000/ mm³
• PLATELETS :
Men and women – 2,50,000-5,00,000/ mm³
• Hb -
Men - 14 –16 g/l
Women - 12 –16 g / l

127. Disorders of blood

128. • RBC disorders
• Anemia
Fe deficiency anemia
Pernicious anemia
Aplastic anemia
• Thalassemia and Sickle cell anemia
• Malaria
• Polycythemia Vera
• WBC disorders
Lymphoma
Leukemia

129. •
•Platelet disorders
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombocytosis
•Plasma disorders
Hemophilia
Von Willebrand disease
Deep venous thrombosis

130. Conclusion
• The Blood is called a fluid Connective Tissue.
.
• Blood is considered a connective tissue for two basic
reasons:
(1) embryologically, it has the same origin (mesodermal) as
do the other connective tissue types and
(2) blood connects the body systems together bringing the
needed oxygen, nutrients, hormones and other signaling
molecules, and removing the wastes.