OLFU-ANTIPOLO CAMPUS

TISSUE &
2ND SEMESTER SY 2023-2024
DR. SONNIE P. TALAVERA WOUND HEALING
PHYSICAL THERAPY
Connective Tissue
most abundant and widely distributed tissues
✓ Functions
✓ Binds body tissues together
✓ Supporting and moving
✓ Protecting
✓ Cushioning and insulating
✓ Storing energy
✓ Conecting tissue to one another
✓ Enclosing and separating tissues
Slide 3.53
Connective Tissue Characteristics

✓ Variations in blood supply

✓ Some tissue types are well vascularized
✓ Some have poor blood supply or are avascular
✓ Extracellular matrix
✓ Non-living material that surrounds living cells

Slide 3.54
CONNECTIVE TISSUE CHARACTERISTICS

CONNECTIVE TISSUES
✓ supports and bind together other structural elements
throughout the body
COMPONENTS

connective tissue cells

✓ mast cells, which intimately surround blood vessels

✓ fibroblasts
✓ resident macrophages
✓ lymphocytes
COMPONENTS

extracellular matrix
✓ structural fibrous proteins (collagen, elastin)
✓adhesive glycoproteins (fibronectin, laminin,
nonfibrillar collagen, tenascin, and others)
COMPONENTS

ground substance

✓gel –like extracellular matrix

✓occupies all space between cells and fibers
✓colorless translucent, highly hydrated gel
✓major component is the GAG
glycosaminoglycans
✓ (heparan sulfate, chondroitin sulfate, and dermatan
sulfate)
COMPONENTS

✓Proteoglycans
✓ core protein linked to one or more polysaccharides
called glycosaminoglycans (GAGs)
✓Hyaluronic acid(HA, hyaluronan or hyaluronate)
✓ are not bound to core protein
✓ .
COMPONENTS
PROTEOGLYCAN
✓Fibronectin
✓ Interconnect the three component of connective
tissues
✓Integrins
✓ Bind collagen fiber directly
✓Laminins
✓ Binding site for cell membrane, collagen fiber and
heparin SO4
✓ Copolymerizes with type IV collagen and entactin to
form basal lamina
COLLAGEN

✓is the most common protein/ MOST BUNDANT

FIBER
✓COLORLESS STRAND
✓Made up tropocollagen which is composed of
a triple helix of three polypeptide α chains,
having a gly-x-y repeating sequence.
Hydroxyproline and hydroxylysine
COLLAGEN
TYPE I
✓ Found in the skin, bone tendon and capsules of organs
✓ Synthesize by fibroblast and also by osteoblast

TYPE II
✓ Found in groundsubstance of catrtilages and nucleus
pulposus of IV disc and vitreous body of the eye
✓ Synthesize by chondrocytes

TYPE III
✓ Found in fiber arranged in loose networks
✓ Synthesized by fibroblast, smooth muscle cells and
hepatocytes
COLLAGEN
TYPE IV
✓Copolymerizes with enactin and laminin
✓Synthesized by epithelial cells

TYPE I- III
✓Are reffered as interstitial collagen fiber

TYPE V- X
✓have restricted
✓Types I, II, III and V, and XI are the interstitial
or fibrillar collagens and the most abundant.
Type IV is nonfibrillar (forms sheets instead
of fibrils) and is the main component of the
BM, together with laminin
✓
RETICULAR FIBER

✓support parenchyma of amany organs

✓typeIII and some glycoprotein
✓silevr stain- agyrop[hilic
✓most abundant in hemopoeitic tissues and
hallow organs
ELASTIC FIBER

✓Stain with resorcin-fuchsin

✓Composed of elastin
✓Desmosine and isodesmosine
✓Synthesize by fibroblast and smooth musclre
of large arteries
✓Seen in IEL internal elastic lamina of medium
sized ateries and in tunica media of large
arteries and parenchyma of alveolus
CONNECTIVE TISSUE FIXED CELLS

✓Stable population of relatively immobile cells

CONNECTIVE TISSUE FIXED CELLS

✓Fibroblast
✓Principal cfell of connective tissues
✓Fusiform tapering on both ends
✓Maybe flat or stellate
✓Principal fxn of synthesis of collagen, elastin
and proteoglycans of ground susbstance
CONNECTIVE TISSUE FIXED CELLS

Adipose cells/ fat cells

✓Arise from mesenchymal cells
✓Take up/store triglycerides
✓Signet ring in appearance- nucleus push to
the periphery by fat globules
CONNECTIVE TISSUE FIXED CELLS

Mesnchymal cells
✓Round stellate
✓Smaller than fibroblast
✓Pluripotent or multipotent-capable of
transforming from one form to another
CONNECTIVE TISSUE FIXED CELLS

Reticular cells
✓Reticular fibers
✓Stellate with long thin cytoplasmic process
✓Some can phagocytosed antigenic materials
and cellular debris
✓Other s can present antigens
CONNECTIVE TISSUE SUBTYPE

Embryonic
✓Mesenchymal
✓Undifferentioated cell/ pluripotent cells
✓Found in developing embryo
✓Inadults- bone marrow and are represented
by adventitial cells
CONNECTIVE TISSUE SUBTYPE

Mucous tissue
✓Few cells and fibers didtributed in abundant
ground substrance chiefly of hyaluronic acid
✓Protects structures against excessive
pressure
✓Wharton’s jelly of the umbnilical cord,
nucleus pulposus of intervertebral disc and
pulp of young teeth
ADULT CONNECTIVE TISSUES

Fibrous

Collagenous
✓Made up of collagen fiber
ADULT CONNECTIVE TISSUES

Loose collagenous
✓Called Areolar tissue
✓Occurs in areas of low resistance is required
✓Collagen fiber are small, moderately
abundant and loosely interwoven
✓Found in lamina propia of stomach, pia mater
( spiunal cord amnd cerebrum), endoneurium,
endomysium, papillary dermis and capsule of
thymus
ADULT CONNECTIVE TISSUES

Dense irregular
✓Fiber are coarse and very abundant with random
orientation
✓Reticular dermis, all capsule except thymus,
epimysium, epiuneurium

Dense regular
✓Fibers are closely packed in parallel bundles
✓Tendons, aponeurosis, ligaments , fascia
ADULT CONNECTIVE TISSUES

Fibrous

Reticular
✓Made up of collagen type III but with
predominance of reticular fiber
✓Forms stroma of bone marrow, spleen, lymph
nodes and thymus
ADULT CONNECTIVE TISSUES

Elastic
✓Elastic fiber predominates
✓Internal elastic membrane of medium sized
artery and tunica media of aorta
ADIPOSE

✓Reserve energy rich materials

2forms

White adipose
✓White to pale yellow dependimng on the
amount of carotenoids
✓insulators
ADIPOSE

✓ Leptin
✓ Controls Apettite center in the brain
✓ Produce hormones that influence CHO and liupid
metabolism
✓ Promotes the growth of capillaries

✓ Resistin
✓ Causes increase resistance to insulinpresent in obese
causing DMII
ADIPOSE
Brown adipose tissues
✓Tan to reddish brownb in color
✓Color due to rich vascularity and in part from
cytochrome in many mitochondria
✓Energy reserve but no insulating function
✓Babie relies on this for heat generation because
of the absence of shivering mechanism
✓Abundant in animals that hibernates
✓ Thermogenin
✓ Uncoupling protein in brown adipose tissue that convert
chemical energy to heat energy
✓SPECIALIZED CONNECTIVE TISSUE
✓Bone
✓Cartilage
✓Blood and lymph
✓Lymphatics
CLINICAL CORRELATION

Ehler Danlos Syndrome-

✓inefficient collagen results in lax ligaments
amnd hyperextensible knee joints

Scleroderma-
✓collagen fiber is made in excess making skin
thick and taut inferring with flexion of fingers
and toes, thickening of wall of esophagus and
excessive fibrosis of body parts
CLINICAL CORRELATION

Osteogenesis Imperfecta
✓Mutation of the gene for type I collagen
resukltiung in abnormal synthesis of alpha or
beta chain of collagen fiber

Scurvy
✓Lack of ascorbic acid that is a cofactor of
proline hydroxylase needed in the synthesis
of collagen. Results in ulceration of gums and
some form of hemorrhage
CLINICAL CORRELATION

Scurvy
✓Lack of ascorbic acid that is a cofactor of
proline hydroxylase needed in the synthesis
of collagen. Results in ulceration of gums and
some form of hemorrhage
TISSUE AND AGING

✓With advance age there is a substantial decrease

in neuron and muscle cell.
✓Collagen fiber become irregular and increase in
number
✓ tendon and ligament to be less flexible and fragile.
✓Elastic fiber become less elastic
✓ decrease flexibility and elasticity of connective tissue
✓ responsible for wrinkling of skin.
INFLAMMATION

✓Occur when tissue is damaged.

✓Inflammation mobilize the body defense, then
isolate and destroy microorganism and foreign
material, so that tissue repair can proceed.
5 CARDINAL SIGNS OF INFLAMMATION

✓Rubor
✓Dolor
✓Calor
✓Tumor
✓Function laesa
INFLAMMATION

Redness and heat

after an injury, chemical substance or mediators are

released in injury and adjacent cell. Some of this
substance causes dilatation of blood vessel causes
an increase the speed of blood cell and substance to
fight infection.
INFLAMMATION

Edema or swelling

increase permeability of blood vessel, allow

material and blood to move out. Where water and
protein move to the tissue. This mechanism help
prevent of infection by forming a wall in the site of
injury.
INFLAMMATION

Pain

where nerve cell ending are stimulated by direct

damage, some substance produce pain and
increase pressure in the tissue.
INFLAMMATION

Disturbance of function

pain, edema and tissue destruction contributes to

loss of function. This warn the person to protect
the injured area from further damage.
CHRONIC INFLAMMATION

✓Prolonged inflammation, when agent

responsible for an injury is not removed or
interfere with the process of healing.
OUTCOME OF CHRONIC
INFLAMMATION:

✓Resolution/regeneration/restitution of normal
structure
✓Repair/organization/healing
✓ connective tissue/fibrosis/scarring
✓It can continue indefinitely--some disease
processes are capable of continuing
indefinitely such as rheumatoid arthritis..
TISSUE REPAIR

✓ Substitution of viable cell for dead cell can

occur by:
a. Regeneration – new cell are the same type as
those that were destroyed and function is
restored.
b. Replacement – new types of tissue developed
and eventually cause scar and loss tissue
function.
TISSUE REPAIR

Cell can be classified into three groups:

a. Labile cell – cell continues to divide throughout
life. E.g. skin and mucous membrane
b. Stable cell – do not actively divide after growth
cease, but divide after injury. E.g. connective
tissue.
c. Permanent cell – no or little ability to divide. E.g.
neuron and skeletal muscle.
RESOLUTION

✓return of tissue to its normal

state.
 FACTORS NECESSARY FOR
RESOLUTION:

✓Removal of the offending agent

✓Regenerative ability if cells have been
destroyed
✓Intact stromal framework
 CATEGORIZATION OF CELLS BASED ON
REGENERATIVE ABILITY:

✓Labile
✓ cells which continue to proliferate throughout life (gut,
skin, bone marrow)
✓Stable cells
✓ cells which retain the capacity to proliferate throughout
life but usually do not unless stimulated (liver, kidney,
pancreas, bone)
✓Permanent cells
✓ cells which cannot reproduce themselves after birth
(neurons, cardiac and skeletal muscle)
 STROMAL FRAMEWORK:

✓It is not enough to be able to regenerate. There

must be an adequate stromal framework.
 Injury

Acute inflammation

Abscess
Chronic inflammation

Resolution Repair
REPAIR

✓aka organization/healing by
connective tissue/fibrosis/scarring
 REPAIR

✓Similar to wound healing

✓Damage to both parenchymal cells and stromal
framework which results in the replacement of
nonregenerated parenchymal cells by connective
tissue which over time produces fibrosis and
scarring.
 GRANULATION TISSUE

✓The early specialized vascular and fibrous

tissue formed is termed granulation tissue.
Grossly it looks pink and granular.
Histologically one sees vessels and
fibroblasts.
 EMBRYONIC STEM CELLS

✓DIFFERENTIATION

✓“KNOCKOUT” MICE (mice raised with specific gene

defects)

✓REPOPULATION OF DAMAGED TISSUES, in

research
 ADULT STEM CELLS

✓MARROW
(HEMOCYTOBLAST)

(hematopoetic stem cells)

✓NON-MARROW
(RESERVE)
MARROW STROMAL CELL
ADULT TISSUE DIFFERENTIATION and REGENERATION
PARALLELS EMBRYONIC DEVELOPMENT
 COMPONENTS NECESSARY FOR
REPAIR

✓Angiogenesis or neovascularization of new

blood vessels
✓Migration and proliferation of fibroblasts
✓Deposition of extracellular matrix (ECM)
✓Remodeling or maturation and organization of
the fibrous tissue
 ANGIOGENESIS
✓BM degradation of parent vessel
✓Migration of endothelial cells toward an
angiogenic stimulus
✓Proliferation of endothelial cells behind the
leading front of migrating cells.
✓Maturation of endothelial cells and
organization into capillary tubes
 MIGRATION AND PROLIFERATION OF
FIBROBLASTS

✓Triggered by many growth factors.

GROWTH FACTORS (GFS)
✓Polypeptides
✓Cytokines
✓LOCOMOTION
✓CONTRACTILITY
✓DIFFERENTIATION
✓ANGIOGENESIS
GROWTH FACTORS (GFS)
✓Epidermal
✓Transforming (alpha, beta)
✓Hepatocyte
✓Vascular Endothelial
✓Platelet Derived
✓Fibroblast
✓Keratinocyte
✓Cytokines (TNF, IL-1, Interferons)
DEPOSITION OF EXTRACELLULAR MATRIX (ECM)

✓Breakdown and deposition of ECM

✓ scar formation and remodeling
✓Fibroblasts
✓ lay down the ECM
✓Metalloproteinases
✓ synthesize and degrade ECM.
✓ tumor metastasis.
REMODELING OR MATURATION AND
ORGANIZATION OF THE FIBROUS TISSUE

Primary component is collagen

✓provides the tensile strength
✓degraded (collagenases)
✓balance of synthesis and degradation which
leads to orderly wound formation.
REMEMBER:

✓"Without collagen, a human being would be

reduced to a clump of cells, interconnected by
a few neurons!"
--Robbins
WOUND HEALING:

Essentially the same as repair.

✓Healing by first intention
✓ (aka primary union)
✓Healing by second intention
✓ (aka secondary union)
IN SECOND INTENTION HEALING
(COMPARED TO FIRST):

✓big hole that needs to be filled in

✓ filled in with abundant granulation tissue

✓With time the wound contracts more than a

wound which healed by first intention.
✓ occurs with the passage of time and is secondary to
myofibroblasts.
 WOUND HEALING
✓1st INTENTION ✓2nd INTENTION

✓Edges lined up ✓Edges NOT lined up

✓Ergo….
✓More granulation
✓More epithelialization
✓MORE FIBROSIS
TIME SCALE FOR REPAIR/WOUND
HEALING:

✓First hours:
✓fibrin clot forms with overlying scab

✓24 hours
✓PMNs appear at margin of incision.
TIME SCALE FOR REPAIR/WOUND
HEALING:
✓24-48 hours:
✓Basal cells at edges proliferate and start to
migrate along the cut margins of the
dermis

✓Day 3
✓Macrophages replace PMNs and
granulation tissue invades incision space.
Epithelial cell proliferation continues.
TIME SCALE FOR REPAIR/WOUND
HEALING:

✓Day 5:
✓Incisional space is filled with granulation
tissue. Neovascularization is maximal.
Collagen fibrils bridge the gap. Epidermis
recovers its normal thickness.
TIME SCALE FOR REPAIR/WOUND
HEALING:
✓2 weeks:
✓Continued proliferation of fibroblasts and
accumulation of collagen. Edema, new
vessels, and inflammatory infiltrates are
absent

✓1 month:
✓Scar covered by intact normal epithelium.
Tensile strength increases with additional
time.
WOUND STRENGTH OVER TIME:

✓At the end of one week wound strength is

approximately 10% of the strength of
unwounded skin
✓It increases rapidly over the next 4 weeks.
✓It peaks at about the 3rd month and achieves
about 70-80% of the tensile strength of
unwounded skin.
From: Coussens: Nature, Volume 420(6917).December 19, 2002.860-867
PATHOLOGIC ASPECTS OF INFLAMMATION AND
WOUND REPAIR

✓Systemic and local host factors influence

the adequacy of the inflammatory-
reparative response.
✓ Protein deficiency
✓ Vitamin deficiency (esp Vit C)
✓ Steroids
✓ Infection is the single most important cause of
delay in healing
✓ Rupture (wound dehiscence)
FIBROSIS/SCARRING
✓DEPOSITION OF COLLAGEN by
FIBROBLASTS
✓With time (weeks, months, years?)
the collagen becomes more dense,
ergo, the tissue becomes
“STRONGER”
 “HEALTHY”
Granulation Tissue
PATHOLOGIC ASPECTS OF INFLAMMATION
AND WOUND REPAIR

✓Aberrations in growth:
✓ Excessive amounts of collagen: keloid
✓ Excessive amounts of granulation tissue: proud
flesh
✓ Uncontrolled proliferation of fibroblasts:
fibromatoses
WOUND RETARDING FACTORS (LOCAL)

✓DECREASED Blood supply

✓Denervation
✓Local Infection
✓FB
✓Hematoma
✓Mechanical stress
✓Necrotic tissue
 WOUND RETARDING FACTORS
(SYSTEMIC)
✓DECREASED Blood supply
✓Age
✓Anemia
✓Malignancy
✓Malnutrition
✓Obesity
✓Infection
✓Organ failure
END GAME