general pathology : Healing of tissues

1. HEALING OF TISSUES
SYAMA M P
THRISSUR GOVERNMENT DENTAL COLLEGE

4. REGENERATION
• Some parenchymal cell are short lived while others have longer life span
• Depending on capacity to divide cells are divided to
1.labile cells: continue to divide throughout life
eg: epithelial cells of epidermis, GIT ,respiratory tract ,cervix vagina endometrium hematopoietic
cells of bone marrow cells of lymph nodes spleen
2.stable cells : Lose their ability to divide after adolescence but retain the ability to divide in response
to a stimuli through out their life
eg: vascular endothelium,fibroblasts, mesenchymal cells like smooth muscle cells bone cartilage cells
parenchymal cells of organs like liver spleen kidney adrenal thyroid
3.parenchymal cells: They lose their ability to proliferate around time of birth
eg: skeletal muscle nervous tissue and cardiac muscle

5. REPAIR
• Replacement of injured tissue by fibrous tissue
• Includes 2 processes
• 1.. Granulation tissue formation
• 2..Contraction of wounds
• GRANULATION TISSUE FORMATION
• Granular : corresponds to new blood vessels with thin covering of fibroblast and
young collagen , which seems to be slightly lifted on the surface
• Pink in colour

6. PHASES OF GRANULATION TISSUE FORMATION
• 1.Phase of inflammation
• 2.Phase of clearance
• 3.Phase of ingrowth of granulation tissue
• a.Angiogenisis
• b. Fibrogenesis

7. ANGIOGENESIS (NEOVASCULARISATION)
• Proliferationof endothelial cells from the margins of severed blood vessels.
• Initially, the proliferated endothelial cells are solid buds
• Within a few hours develop a lumen and start carrying blood.
• The newly formed blood vessels are more leaky, accounting for the oedematous appearance of new granulation
tissue.
• Soon, these blood vessels differentiate into musculararterioles, thin-walled venules and true capillaries.
• The process of angiogenesis is stimulated with proteolytic destruction of basement membrane.
• Angiogenesis takes place under the influence of following factors:
• a) Vascular endothelial growth factor (VEGF) bymesenchymal cells
• b) Platelet-derived growth factor (PDGF)
• c)Transforminggrowth factor-ß (TGF-B)
• d)Basic fibroblast growth factor(bFGF)
• e) Surface integrins are all associated with cellularproliferation.

8. ANGIOGENESIS (NEOVASCULARISATION)

9. FIBROGENISIS
• The newly formed blood vessels are present in an amorphous ground substance or matrix.
• The new fibroblasts have features intermediate between those of fibroblasts and smoothmuscle
cells (myofibroblasts).
• Collagenfibrils begin to appear by about 6th day.
• The myofibroblasts have surface receptors for fibronectin molecules which form bridges
between collagen fibrils.
• As maturation proceeds,more and more collagen is formed while the number of active
fibroblasts and new blood vessels decreases.
• This results information of inactive looking Scar
• This process is known as cicatrisation.

10. PRIMARY UNION
• This is defined as healing of a wound wlhich has the followingcharacteristics:
• i) clean and uninfected;
• ii) surgically incised;
• ii) without much loss of cells and tissue;
• iv) edges of wound are approximated by surgical sutures.
• 1.. Initial haemorrhage Immediately after injury, theSpace between the approximated surfaces of incised woundis filled with blood which then clots and seals the woundagainst dehydration and infection
• .2. Acute inflammatory response This occurs within24 hours with appearance of polymorphs from the marginsof incision. By 3rd day, polymorphs are replaced bymacrophages.
• 3. Epithelial changes Basal cells of epidermis from boththe cut margins start proliferating and migrating towardsincisional space in the form of epithelial spurs. A well-approximated wound is covered by a
layer of epithelium in48 hours. The migrated epidermal cells separate theunderlying viable dermis from the overlying necrotic materialand clot, forming Scab which is cast off. The basal cells fromthe
margins continue to divide. By 5th day, a multilayered newepidermis is formed which is differentiated into superficialand deeper layers.
• 4. Organisation By 3rd day, fibroblasts also invade thewound area. By 5th day, new collagen fibrils start formingwhich dominate till healing is completed. In 4 weeks, theScar tissue with scanty cellular and
vascular elements, a fewinflammatory cells and epithelialised surface is formed.

12. • 5. Suture tracks
• Each suture track is a separate wound and incites the same phenomena as in healing of
theprimary wound
• When sutures are removed around 7th day, much of epithelialised suture track is avulsed and
the remaining epithelial tissue in the track is absorbed.
• However, sometimes the suture track gets infected (stitch abscess), or the epithelial cells may
persist in the track(implantation or epidermal cysts).
• Thus, the scar formed in a sutured wound is neat due to close apposition of the margins of
wound; the use of adhesive tapes or metal clips avoids removal of stitches and its complications.

13. HEALING BY SECOND INTENTION (SECONDARY
UNION)
• This is defined as healing of a wound having the followingcharacteristics
• :open with a large tissue defect, at times infected;n
• having extensive loss of cells and tissues;
• the wound is not approximated by surgical sutures but isleft open.
• Healing takes place from the base upwardand also from the margins inwards.
Healing by second intention is slow and results in a large, at times ugly, scar as
compared to rapid healing and neat scar of primarv union)

14. • 1. Initial haemorrhage
• 2.Inflammatory response
• . Epithelial changes :As in primary healing, the epidermal cells from both the margins ol wound
proliferateand migrate into the wound in the form of epithelial spurs till they meet in the middle
and re-epithelialise the gapcompletely
• . However, the proliferating epithelial cells do not cover the surface fully until granulation tissue
from base has started filling the wound space. I
• n this way, pre-existing viableconnective tissue is separated from necrotic material and clot on
the surface, forming scab which is cast off
• In time, there generated epidermis becomes stratified and keratinised.

15. • 4. Granulation tissue
• Main bulk of secondary healing is by granulations.
• The newly-formed granulation tissue is deep red,granular and very fragile.
• With time, the scar on maturation becomes pale and white due to increase in collagen and decrease in vascularity.
• Specialised structures of the skin like hair follicles and sweat glands are not replaced unless theirviable residues
remain which may regenerate
• .5. Wound contraction Contraction of wound is an important feature of secondary healing, not seen in
primaryhealing.
• Due to the action of myofibroblasts present in granulation tissue, the wound contracts to one-third to one-fourth of
its original size.

16. • 6.Presence of infection Bacterial contamination lead to necrosis suppuration
thrombosis
• Surgical removal of dead and necrosis tissue debridement help in preventing this
• COMPLICATIONS OF WOUND HEALING
• 1. Infection The wound may get infected due to entry bacteria which delays the
healing.
• 2. Implantation (epidermal) cyst Formation of implantaticepidermoid cyst may
occur due to persistence of epithelial cells in the wound after healing
• .3. Pigmentation Healed wounds may at times have rust-like colour due to
staining with haemosiderin.

17. • Some coloured particulate material left in the wound may persist and impart colour to the healed
wound
• 4. Deficient scar formation This may occur due to inadequate formation of granulation tissue.
• 5. Incisional hernia A weak scar, especially after a laparotomy, may be either the site of bursting open
of a wound early (wound dehiscence), or later an incisional hernia may occur at this site
• .6. Hypertrophied scars and keloid formation At times,the scar formed is excessive, ugly and painful.
Excessive formation of collagen in healing may result in keloid(claw-like) formation, seen more
commonly in blacks .Hypertrophied scars differ from keloid in that they areconfined to the borders of
the initial wound while keloid have tumour-like projection of connective tissue.
• 7. Excessive contraction An exaggeration of wound contraction may result in formation of contractures
or cicatrisation e.g. Dupuytren's (palmar) contracture, plantar contracture and Peyronies disease
• Neoplasia

18. FRACTURE HEALING

19. BASED ON STABILITY
PRIMARY UNION OF FRACTURES
• Small amount of strain below 2% then it heals
by primary union
• They can be approximated by compression
clamps and metal plates
• No procallus formation only osseous callus
formation and then remodelling
• More extensive bone necrosis
• Slow healing
SECONDARY UNION OF
FRACTURES
• Strain from 2% to 10 %
• Part is immobilized by plaster cast
• It’s a continuous process
• Fast healing
• 1.Procallus formation
• 2. Osseous callus formation
• 3. Remodelling

21. PROCALLUS FORMATION
• Hematoma • Local inflammatory response
• From the leaky blood vessels
Exudation of fibrin polymorph and
macrophages
• Macrophages clears all the debris
• Fragments of enclosed bone
removed by osteoclasts and
macrophages

22. • INGROWTH OF GRANULATION TISSUE
• Begins with neovascularisation
• Then proliferation of mesenchymal cells
• Mesenchymal cells are multi potent stem cells that can differentiate and form
chondrocytes osteoblasts
• They are from periosteum and endosteum
• Thus soft tissue callus is formed they unite the fractured ends

23. • 4 Callus composed of woven boneand cartilage
• Startswithin the first few days
• The cells of inner layer of the periosteum have osteogenic potential and lay down collagenas well as
osteoid matrix in the granulation tissue
• .The osteoid undergoes calcification and is called woven bone callus.
• A much wider zone over the cortex on either side of fractured ends is covered by the woven bone
callus and united to bridge the gap between the ends, giving spindle-shapedor fusiform appearance to
the union.
• In poorly immobilised fractures (e.g. fracture ribs), the.subperiosteal osteoblasts may form cartilage at
the fracture site. At times, callus is composed of woven bone as well as cartilage, temporarily
immobilising the bone ends.

24. • The procallus has external intermediate and internal procallus

25. OSSEOUS CALLUS FORMATION
• Procallus act as scaffolding on which osseous callus with lamellar bone is
formed
• Osteoclasts will clear away woven bone
• Calcified cartilage disintegrates
• In that place new blood vessels and osteoblasts invade
• They lay down osteoid that is calcified and lamellar bone is formed

26. REMODELLING
• During the formation of lamellar bone,Osteoblastic laying and osteoclastic
removal are taking place remodelling the united bone ends, which after
sometime, is indistinguishable from the normal bone
• External callus cleared away
• Intermediate callus become cortex
• Internal callus become bone marrow