Connective Tissue. Structural Shape and organization Defense Immunoinflammatory response ...

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*****

http://raven.zoology.washington.edu/embryos/auximages/dendraster_mes.blastula3.jpg

Component of Connective Tissue

Cells Fibers Ground Substance

5

FibersFibers

Collagen fibers Reticular fibers

Elastic fibers

Collagen fibers Reticular fibers

Elastic fibers

Proteins polymersProteins polymers

6

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

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.

12

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


Fibroblasts

Pericytes

Mast cell

Macrophages

Adipose cells (Fat cells)

Fibroblasts

Pericytes

Mast cell

Macrophages


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



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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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Fibroblasts

Pericytes

Mast cell

Macrophages


Fibroblasts

Pericytes

Mast cell

Macrophages


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)

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30










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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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do

Och

oa-V

arga

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Ger

ard

o O

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-Var

gas

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

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61Mast cell

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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.

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)


Table 4.1 Comparison of Classes of Connective Tissues (2 of 2)


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


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


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


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


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


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


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).


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


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


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


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


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



Adipose tissue

fat



Dense connective tissue

tendons; ligaments



Hyaline cartilage

nose; ends of long bones; ribs



Elastic cartilage

outer ear; epiglottis



Fibrocartilage

between vertebrae; knee joints; pubic joint



Bone

skeletal system



Blood

bloodstream

Connective Tissue. Structural Shape and organization Defense Immunoinflammatory response ...

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