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Connective TissueConnective Tissue
Functions of Connective Tissue
Structural Shape and organization
Defense Immunoinflammatory response
Nutrition Blood vessels
Storage Lipids in adipocytes are the major energy
depot in the body
Origins of CT
Mesenchyme Embryonic tissue, undifferentiated Develops from mesoderm Cells migrate from origins, penetrate
and surround organs Develop into other types of structures:
blood cells, muscles, bones ****Mesodermal cells migrate from their
site of origin,sorrounding and penetrating organs.These are MESENCHYMAL CELLS*****
Component of Connective Tissue
Cells Fibers Ground Substance
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FibersFibers
Collagen fibers Reticular fibers
Elastic fibers
Collagen fibers Reticular fibers
Elastic fibers
Proteins polymersProteins polymers
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CollagenCollagen
Type IOrgan capsules, bone, dentin, tendon, dermis, scars
Type IIHyaline & elastic cartilage, vitreous in eye. notochord
Type IIIUsually associated with other types of collagen
Type IVBasal lamina (it does not form fibers), lens of eye
Type VFetal membranes and some small vessels
Type IOrgan capsules, bone, dentin, tendon, dermis, scars
Type IIHyaline & elastic cartilage, vitreous in eye. notochord
Type IIIUsually associated with other types of collagen
Type IVBasal lamina (it does not form fibers), lens of eye
Type VFetal membranes and some small vessels
Most abundant protein in human bodyMost abundant protein in human body
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8
90.87 nm
Glycine
Every third amino acid in the α chain
Usually proline follows (“X” ) in the chain
Usually hydroxyproline or hydroxylysine (“Y” ) precede glycine in the chain
Glycine Glycine
Proline
Hydroxy
proline
Proline
YY
X
Abnormalities of collagen
Procollagen
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collagen
GlycineHydroxyprolineHydroxylysine
prolinelysine
Vit C as a cofactor
Scurvy:Produced by deficiency of Vit C which is a cofactor of prolylhydroxylase and lysylhydroxylase.Blood vessels rupture, wounds fail to heal, gum ulceration.
Abnormal accumulation of collagen
Sclerosis, fibrosis of organs causing hardening & loss of function.
Keloid – local swelling caused by abnormal amounts of collagen in scar tissue.
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Usually Type I collagen
Osteogenesis Imperfecta:
Genetic disorder that affects the formation of collagen (specially type I).
4 types of disease entities that vary in severity.
Leads to fragile bones which are prone for repeated fractures, teeth abnormalities, lax joints & hearing loss.
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Ehlers Danlos Syndromes
Group of heritable connective tissue disorders
Cutaneous findings – hyperextensible and fragile skin, poor wound healing, easy bruising, molluscoid pseudotumors
Systemic features – joint hypermobility, scoliosis, significant risk of spontaneous arterial, intestinal or uterine rupture
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Ehlers Danlos Syndromes Genetic disorders
(Autosomal dominant) involving defect in the collagen. (Type III procollagen)
12 variants of disease observed
Type IV is greatest risk for aortic rupture because the normal aorta is rich in type III procollagen
Characteristics:– Skin Hyperelasticity– Hypermobile joints
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structural integrity and function of tissues
requiring reversible extensibility or deformability
high levels in tissues that require elasticity
E.g: lung, skin, major blood vessels
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Elastic Fibers - functionElastic Fibers - function
Elastic Fiber System
Elastin: rich in proline and lysine Glycine randomly distributed
– hydrophobic, random coiling
Desmosine and isodesmosinefor covalent bonding of elastin molecules
Form thick fibers or lamellar sheets (as in elastic arteries)
Fibrillin-1: Glycoprotein that form
microfibrils Absence of fibrillin
microfibrils leads to lost of elastin lamellae in blood vessels
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Marfan Syndrome
Mutations in the fibrillin gene (FBN1) cause defective elastic fiber formation.
Autosomal dominant disorder
Lack of resistance in tissues rich in elastic fibers.
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Marfan’s syndrome - Characteristics
1. Aortic aneurysm or dissection often occurring at the base of the aorta
2. Dislocation of lenses: Vision issues
3. Long thin extremities
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Reticular FibersReticular Fibers
Organs that quickly change shape and volumeOrgans that quickly change shape and volume
Spleen, lymph nodes, liverSpleen, lymph nodes, liver
0.5 – 2 µm in diameter
Form a network
PAS positive
Mainly made by type III collagen
0.5 – 2 µm in diameter
Form a network
PAS positive
Mainly made by type III collagen
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Reticular fibers
21Reticular fibers
Ehlers Danlos Syndrome type IV
Faulty transcription or translation of type lll colagen
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Fixed/Resident Cells of Connective Tissue
Fixed/Resident Cells of Connective Tissue
Fibroblasts
Pericytes
Mast cell
Macrophages
Adipose cells (Fat cells)
Fibroblasts
Pericytes
Mast cell
Macrophages
Adipose cells (Fat cells)
Mesenchymal Cells
Multipotential cells (also known as mesenchymal stem cells)
Polyhedral, heterogeneous and pleomorphic
Often stellate in appearance
Long oval nucleus No fibers in ECM
24Seen in developing organisms (embryos and fetuses)
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Fibroblast – Fibrocyte systemFibroblast – Fibrocyte system
The fibroblast synthesizes the fibers and the amorphous substance
The fibrocyte is the mature or resting form of the fibroblast
The fibroblast synthesizes the fibers and the amorphous substance
The fibrocyte is the mature or resting form of the fibroblast
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Fibroblast – Fibrocyte systemFibroblast – Fibrocyte system
Produce growth factors that influence cell growth & differentiation.
Healing of connective tissue.
Myofibroblasts – Have features of fibroblasts & smooth muscle cells. Contain high quantities of contractile microfilaments (actin & myosin)
Involved in wound contraction
Produce growth factors that influence cell growth & differentiation.
Healing of connective tissue.
Myofibroblasts – Have features of fibroblasts & smooth muscle cells. Contain high quantities of contractile microfilaments (actin & myosin)
Involved in wound contraction
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Fixed/Resident Cells of Connective Tissue
Fixed/Resident Cells of Connective Tissue
Fibroblasts
Pericytes
Mast cell
Macrophages
Adipose cells (Fat cells)
Fibroblasts
Pericytes
Mast cell
Macrophages
Adipose cells (Fat cells)
Mesenchymal Cells
Multipotential cells (also known as mesenchymal stem cells)
Polyhedral, heterogeneous and pleomorphic
Often stellate in appearance
Long oval nucleus No fibers in ECM
28Seen in developing organisms (embryos and fetuses)
29
Fibroblast – Fibrocyte systemFibroblast – Fibrocyte system
The fibroblast synthesizes the fibers and the amorphous substance
The fibrocyte is the mature or resting form of the fibroblast
The fibroblast synthesizes the fibers and the amorphous substance
The fibrocyte is the mature or resting form of the fibroblast
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Fibroblast – Fibrocyte systemFibroblast – Fibrocyte system
Produce growth factors that influence cell growth & differentiation.
Healing of connective tissue.
Myofibroblasts – Have features of fibroblasts & smooth muscle cells. Contain high quantities of contractile microfilaments (actin & myosin)
Involved in wound contraction
Produce growth factors that influence cell growth & differentiation.
Healing of connective tissue.
Myofibroblasts – Have features of fibroblasts & smooth muscle cells. Contain high quantities of contractile microfilaments (actin & myosin)
Involved in wound contraction
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Adipose TissueAdipose Tissue
Represents 15-20 % of male normal weight 20-25 % of female normal weight
Store triglycerides energyMechanical shock absorbersThermal insulationBody shapeArchitecture
Represents 15-20 % of male normal weight 20-25 % of female normal weight
Store triglycerides energyMechanical shock absorbersThermal insulationBody shapeArchitecture
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Types of Adipose TissueTypes of Adipose TissueUnilocularUnilocular
common or yellow fatcommon or yellow fat
brown (fetal) fatbrown (fetal) fat
MultilocularMultilocular
White AdipocyteWhite Adipocyte Brown adipocyteBrown adipocyte
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Types of Adipose TissueTypes of Adipose Tissue
UnilocularUnilocular MultilocularMultilocular120 µmOne big fat
vacuoleMain energy
depositYellow with
carotenoids
120 µmOne big fat
vacuoleMain energy
depositYellow with
carotenoids
Smaller than unilocular fat cells (25-40 µm)
Highly innervated
Produce heat quickly
Smaller than unilocular fat cells (25-40 µm)
Highly innervated
Produce heat quickly
Adipose Tissue WAT: synthesize the enzyme
lipoprotein lipase which hydrolyses -VLDL and chylomicrons into FFA and glycerol
FFA enter the adipose cell as TG Lipid storage is modulated by
insulin, neural impulses/adrenaline and lipase
BAT: generating heat by uncoupling oxidative phophorylation: Thermogenin
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35Adipocytes
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Adipocytes and connective tissue
37Brown adipocytes
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ObesityObesity• High blood pressure, hypertension • High blood cholesterol, dyslipidemia • Type 2 (non-insulin dependent) diabetes • Insulin resistance, glucose intolerance • Hyperinsulinemia • Coronary heart disease • Angina pectoris • Congestive heart failure • Stroke • Gallstones• Cholescystitis and cholelithiasis • Gout • Osteoarthritis • Obstructive sleep apnea and respiratory problems • Some types of cancer (such as endometrial, breast, prostate, and colon) • Complications of pregnancy • Poor female reproductive health (such as menstrual irregularities, infertility, irregular
ovulation) • Bladder control problems (such as stress incontinence) • Uric acid nephrolithiasis • Psychological disorders (such as depression, eating disorders, distorted body image, and
low self esteem)
• High blood pressure, hypertension • High blood cholesterol, dyslipidemia • Type 2 (non-insulin dependent) diabetes • Insulin resistance, glucose intolerance • Hyperinsulinemia • Coronary heart disease • Angina pectoris • Congestive heart failure • Stroke • Gallstones• Cholescystitis and cholelithiasis • Gout • Osteoarthritis • Obstructive sleep apnea and respiratory problems • Some types of cancer (such as endometrial, breast, prostate, and colon) • Complications of pregnancy • Poor female reproductive health (such as menstrual irregularities, infertility, irregular
ovulation) • Bladder control problems (such as stress incontinence) • Uric acid nephrolithiasis • Psychological disorders (such as depression, eating disorders, distorted body image, and
low self esteem)
CLINICAL CASE A 67-year-old man visited our clinic with a two week
history of persistent paroxysmal cough. Clinical symptoms, such as sneezing, rhinorrhea, itchy nose and eyes, urticaria, and cough had occurred since he was 40 years of age while working in the cornfield, particularly in July through August when the flowers blossomed. These clinical symptoms were improved upon resting outside the cornfield. He had worked as a professional farmer in corn and potato fields since he was 26 years of age. The corn cultivation area was 6,600 m2.
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IMMUNE REACTION TO ALLERGIES
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MacrophageMacrophage
Also known as mononuclear phagocyte and histiocyte
Phagocytic capacity Become larger (epithelioid cells) if stimulated,
and even fuse with each other to form giant multinucleated cells
Very important in the immunoinflammatory response
Receives different names depending on its location
Also known as mononuclear phagocyte and histiocyte
Phagocytic capacity Become larger (epithelioid cells) if stimulated,
and even fuse with each other to form giant multinucleated cells
Very important in the immunoinflammatory response
Receives different names depending on its location
Kupffer cells — liverMesangial cells — kidneyMicroglia — central nervous system
Kupffer cells — liverMesangial cells — kidneyMicroglia — central nervous system
Macrophages are the first cells that encounter antigens
- present the antigen to lymphocytes are thymocytes for destruction ( antigen presenting cells)
Phagocytic activity of the macrophages-involution in the uterus.(post-paturition).
In pathological conditions macrophages fuse to form multicellular giant cells
Which in certain clinical conditions are diagnostic for certain diseases.
44Monocyte - precursor
Macrophages: Biological Scavengers
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Low power High power
Macrophages are easily identified when the animal has been injected with coal, India ink, carbon or other similar type particles.
46Low power High power
47© School of Biological and Life Sciences University of Surrey, Guildford
Macrophage
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Transient Connective Tissue CellsTransient Connective Tissue Cells
Lymphocytes
Plasma cells
Leukocytes
Lymphocytes
Plasma cells
Leukocytes
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LeukocytesLeukocytes
Five types
Irregular nucleiNeutrophils, eosinophils, basophils
Regular nucleiMonocytes, lymphocytes
Five types
Irregular nucleiNeutrophils, eosinophils, basophils
Regular nucleiMonocytes, lymphocytes
Defense cells
50© Gerardo Ochoa-Vargas
Blood
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Neutrophil Neutrophil Eosinophil Eosinophil
Basophil Basophil LymphocyteLymphocyte MonocyteMonocyte
Blood Cells
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Plasma CellsPlasma CellsActivated B lymphocytesProduce antibodies (immunoglobulins) Mean life 10-20 daysProminent Golgi complex and RER
Activated B lymphocytesProduce antibodies (immunoglobulins) Mean life 10-20 daysProminent Golgi complex and RER
Nucleus is eccentrically placed possessing clumps of heterochromatin which have a characteristic spoke wheel appearance
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Plasma cells
54Plasma cell
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Mast CellsMast Cells
20 – 30 µm diameter
Basophilic granules 0.3 – 2.0 µm diameter, full with heparin and histamine
Release eosinophil chemotactic factor of anaphylaxis (ECF-A), the slow-reacting substance of anaphylaxis and leukotrienes
20 – 30 µm diameter
Basophilic granules 0.3 – 2.0 µm diameter, full with heparin and histamine
Release eosinophil chemotactic factor of anaphylaxis (ECF-A), the slow-reacting substance of anaphylaxis and leukotrienes
56
Mast CellsMast Cells
Two populations Connective tissue mast cells – more common,
near the blood vessels.
Mucosal mast cells – less common, associated with respiratory and digestive mucosae.
Two populations Connective tissue mast cells – more common,
near the blood vessels.
Mucosal mast cells – less common, associated with respiratory and digestive mucosae.
Dermis, digestive and respiratory tractsDermis, digestive and respiratory tracts
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Mast cells
Mast Cells: Histology
58Low power High Power
Mast Cells Histology Large, oval cells Basophilic/
metachromatic granules Coarse, dense granulesFunction Anaphylactic response to
hyperallergic reactionsProducts heparin (sometimes) histamine eosinophil chemotactic
factor of anaphylaxis (ECF-A)
Leukotrienes (not stored)59
Mast Cell Ultrastructure
Electron dense granules
Cytoplasm packed with granules
Euchromatic nucleus
rER Prominent Golgi Elaborate
plasmalemma
60
61Mast cell
62
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Mast cells & Hypersensitivity Reactions Mast cells & Hypersensitivity Reactions
Mast cells release their contents in response to an allergen (rhinitis, asthma)
Anaphylactic shock – Massive amounts of mediator release in response to toxic substance. Contents released from mast cells cause bronchoconstriction (difficulty breathing), vasodilation (shock) & increased capillary permeability.
Mast cells release their contents in response to an allergen (rhinitis, asthma)
Anaphylactic shock – Massive amounts of mediator release in response to toxic substance. Contents released from mast cells cause bronchoconstriction (difficulty breathing), vasodilation (shock) & increased capillary permeability.
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© T
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The following types of connective tissue are covered in this activity:
1. Loose (areolar) connective tissue (delicate thin layers between
tissues; present in all mucous membranes)
2. Adipose tissue (fat)
3. Dense connective tissue (tendons/ligaments)
4. Hyaline cartilage (nose/ends of long bones/ribs)
5. Elastic cartilage (outer ear/epiglottis)
6. Fibrocartilage (between vertebrae/knee joints/pubic joint)
7. Bone (skeletal system)
8 Blood (bloodstream)
Copyright © 2010 Pearson Education, Inc.
Table 4.1 Comparison of Classes of Connective Tissues (1 of 2)
Copyright © 2010 Pearson Education, Inc.
Table 4.1 Comparison of Classes of Connective Tissues (2 of 2)
Copyright © 2010 Pearson Education, Inc.
Figure 4.8a Connective tissues.
(a) Connective tissue proper: loose connective tissue, areolar
Description: Gel-like matrix with allthree fiber types; cells: fibroblasts,macrophages, mast cells, and somewhite blood cells.
Function: Wraps and cushionsorgans; its macrophages phagocytizebacteria; plays important role ininflammation; holds and conveystissue fluid.
Location: Widely distributed underepithelia of body, e.g., forms laminapropria of mucous membranes;packages organs; surroundscapillaries.
Photomicrograph: Areolar connective tissue, asoft packaging tissue of the body (300x).
Epithelium
Laminapropria
Fibroblastnuclei
Elasticfibers
Collagenfibers
Copyright © 2010 Pearson Education, Inc.
Figure 4.7 Areolar connective tissue: A prototype (model) connective tissue.
Macrophage
Fibroblast
Lymphocyte
Fat cell
Mast cell
Neutrophil
Capillary
Cell types Extracellularmatrix
Fibers• Collagen fiber• Elastic fiber• Reticular fiber
Ground substance
Copyright © 2010 Pearson Education, Inc.
Figure 4.8b Connective tissues.
(b) Connective tissue proper: loose connective tissue, adipose
Description: Matrix as in areolar,but very sparse; closely packedadipocytes, or fat cells, havenucleus pushed to the side by largefat droplet.
Function: Provides reserve foodfuel; insulates against heat loss;supports and protects organs.
Location: Under skin in thehypodermis; around kidneys andeyeballs; within abdomen; in breasts.
Photomicrograph: Adipose tissue from thesubcutaneous layer under the skin (350x).
Nucleus offat cell
Vacuolecontainingfat droplet
Adiposetissue
Mammaryglands
Copyright © 2010 Pearson Education, Inc.
Figure 4.8c Connective tissues.
(c) Connective tissue proper: loose connective tissue, reticular
Description: Network of reticularfibers in a typical loose groundsubstance; reticular cells lie on thenetwork.
Function: Fibers form a soft internalskeleton (stroma) that supports othercell types including white blood cells,mast cells, and macrophages.
Location: Lymphoid organs (lymphnodes, bone marrow, and spleen).
Photomicrograph: Dark-staining network of reticularconnective tissue fibers forming the internal skeletonof the spleen (350x).
Spleen
White bloodcell(lymphocyte)
Reticularfibers
Copyright © 2010 Pearson Education, Inc.
Figure 4.8d Connective tissues.
(d) Connective tissue proper: dense connective tissue, dense regular
Description: Primarily parallelcollagen fibers; a few elastic fibers;major cell type is the fibroblast.
Function: Attaches muscles tobones or to muscles; attaches bonesto bones; withstands great tensilestress when pulling force is appliedin one direction.
Location: Tendons, mostligaments, aponeuroses.
Photomicrograph: Dense regular connectivetissue from a tendon (500x).
Shoulderjoint
Ligament
Tendon
Collagenfibers
Nuclei offibroblasts
Copyright © 2010 Pearson Education, Inc.
Figure 4.8e Connective tissues.
(e) Connective tissue proper: dense connective tissue, dense irregular
Description: Primarilyirregularly arranged collagenfibers; some elastic fibers;major cell type is the fibroblast.
Function: Able to withstandtension exerted in manydirections; provides structuralstrength.
Location: Fibrous capsules oforgans and of joints; dermis ofthe skin; submucosa ofdigestive tract.
Photomicrograph: Dense irregularconnective tissue from the dermis of theskin (400x).
Collagenfibers
Nuclei offibroblasts
Fibrousjointcapsule
Copyright © 2010 Pearson Education, Inc.
Figure 4.8f Connective tissues.
(f) Connective tissue proper: dense connective tissue, elastic
Description: Dense regularconnective tissue containing a highproportion of elastic fibers.
Function: Allows recoil of tissuefollowing stretching; maintainspulsatile flow of blood througharteries; aids passive recoil of lungsfollowing inspiration.
Location: Walls of large arteries;within certain ligaments associatedwith the vertebral column; within thewalls of the bronchial tubes.
Elastic fibers
Aorta
HeartPhotomicrograph: Elastic connective tissue inthe wall of the aorta (250x).
Copyright © 2010 Pearson Education, Inc.
Figure 4.8g Connective tissues.
(g) Cartilage: hyaline
Description: Amorphous but firmmatrix; collagen fibers form animperceptible network; chondroblastsproduce the matrix and when mature(chondrocytes) lie in lacunae.
Function: Supports and reinforces;has resilient cushioning properties;resists compressive stress.
Location: Forms most of theembryonic skeleton; covers the endsof long bones in joint cavities; formscostal cartilages of the ribs; cartilagesof the nose, trachea, and larynx.
Photomicrograph: Hyaline cartilage from thetrachea (750x).
Costalcartilages
Chondrocytein lacuna
Matrix
Copyright © 2010 Pearson Education, Inc.
Figure 4.8h Connective tissues.
(h) Cartilage: elastic
Description: Similar to hyalinecartilage, but more elastic fibersin matrix.
Function: Maintains the shapeof a structure while allowinggreat flexibility.
Location: Supports the externalear (pinna); epiglottis.
Photomicrograph: Elastic cartilage fromthe human ear pinna; forms the flexibleskeleton of the ear (800x).
Chondrocytein lacuna
Matrix
Copyright © 2010 Pearson Education, Inc.
Figure 4.8i Connective tissues.
(i) Cartilage: fibrocartilage
Description: Matrix similar tobut less firm than that in hyalinecartilage; thick collagen fiberspredominate.
Function: Tensile strengthwith the ability to absorbcompressive shock.
Location: Intervertebral discs;pubic symphysis; discs of kneejoint.
Photomicrograph: Fibrocartilage of anintervertebral disc (125x). Special stainingproduced the blue color seen.
Intervertebraldiscs
Chondrocytesin lacunae
Collagenfiber
Copyright © 2010 Pearson Education, Inc.
Figure 4.8j Connective tissues.
(j) Others: bone (osseous tissue)
Description: Hard, calcifiedmatrix containing many collagenfibers; osteocytes lie in lacunae.Very well vascularized.
Function: Bone supports andprotects (by enclosing);provides levers for the musclesto act on; stores calcium andother minerals and fat; marrowinside bones is the site for bloodcell formation (hematopoiesis).
Location: Bones
Photomicrograph: Cross-sectional viewof bone (125x).
Lacunae
Lamella
Centralcanal
Copyright © 2010 Pearson Education, Inc.
Figure 4.8k Connective tissues.
(k) Others: blood
Description: Red and whiteblood cells in a fluid matrix(plasma).
Function: Transport ofrespiratory gases, nutrients,wastes, and other substances.
Location: Contained withinblood vessels.
Photomicrograph: Smear of human blood (1860x); twowhite blood cells (neutrophil in upper left and lymphocytein lower right) are seen surrounded by red blood cells.
Neutrophil
Red bloodcells
Lymphocyte
Plasma
BASED ON THE ABOVE SLIDES
Can you name?
First, the tissue type
Second, where in the body the tissue is found
What kind of tissue does this represent?
Where in the body can you find this tissue?
delicate thin layers between tissues; present in all mucous membranes
Loose (areolar) connective tissue
What kind of tissue does this represent?
Where in the body can you find this tissue?
Adipose tissue
fat
What kind of tissue does this represent?
Where in the body can you find this tissue?
Dense connective tissue
tendons; ligaments
What kind of tissue does this represent?
Where in the body can you find this tissue?
Hyaline cartilage
nose; ends of long bones; ribs
What kind of tissue does this represent?
Where in the body can you find this tissue?
Elastic cartilage
outer ear; epiglottis
What kind of tissue does this represent?
Where in the body can you find this tissue?
Fibrocartilage
between vertebrae; knee joints; pubic joint
What kind of tissue does this represent?
Where in the body can you find this tissue?
Bone
skeletal system
What kind of tissue does this represent?
Where in the body can you find this tissue?
Blood
bloodstream