TISSUE REPAIR & WOUND HEALING DR. SALEEM SHAIKH 1. what is inflammation? Write the types and signs of inflammation. Explain in detail about the events in acute inflamm 2. Define neoplasia? Enumerate the types of neoplasia. Explain in detail the characteristic of neoplasia. INTRODUCTION Healing is the body response to injury in an attempt to restore normal structure and function. Healing involves two distinct processes: Regeneration: healing takes place by proliferation of parenchymal cells and usually results in complete restoration of the original tissues Repair: healing takes place by proliferation of connective tissue elements resulting in fibrosis and scarring. Both the processes may take place simultaneously. REGENERATION & REPAIR Some cells of the body have a short life span whereas others may have a longer life span. In order to maintain the proper function of the tissues the cells are under constant control of growth factors, which regulate their cell cycle. Some mature cells of the body do not divide at all, while some cells complete a cell cycle in 16-24 hrs. Depending on their capacity to divide the cells can be grouped onto 3 categories: Labile cells Stable cells Permanent cells REGENERATION & REPAIR Labile cells: these cells continue to multiply throughout life under normal physiologic conditions. Eg – epithelial cells of epidermis, respiratory tract and cervix, haematopoietic cells of bone marrow and cells of lymph nodes and spleen Stable cells: these cells lose their ability to multiply after maturity but retain the capacity to multiply in response to stimuli throughout adult life. Eg – parenchymal cells of liver, pancreas and kidney, fibroblast, smooth muscle cells. Permanent cells: these cells lose their ability to proliferate around the time of birth. Eg – neurons, cardiac muscle cells. Labile and stable cells have more chance of healing by regeneration, whereas permanent cells heal by repair. WOUND HEALING Healing of skin and mucosal wounds provides a classical example of combination of repair and regeneration. Wound healing can be accomplished by to ways – Healing by first intention (primary union) Healing by second intention (secondary union) Healing by first intention (primary union): this is a wound which is Clean and uninfected Surgically incised Without much loss of tissue or cells Edges of the wound are approximated by surgical sutures. Healing by first intention (primary union) Stages of primary healing: 1. Initial haemorrhage: Immediately after injury, the space is filled with blood which then clots and seals the wound against dehydration and infection. 2. Acute inflammatory response: Initially neutrophils appear at the site of injury, which are replaced by macrophages by the 3rd day. 3. Epithelial changes: the basal cells of the epidermis proliferate from the cut margins and migrate towards the incisional space. The migrating epithelial cells separate the underlying normal connective tissue from the overlying necrotic material and clot. A well approximated wound gets covered by epithelium in 48 hrs. Healing by first intention (primary union) 4. Organisation: by the 3rd day fibroblasts also invade the wound area. By 5th day, new collagen fibrils start forming, which continue to form till healing is completed. Suture tracks: each suture track is a separate wound and incites the same phenomena as in healing of wounds. If the sutures are removed after 1 week much of the epithelised track is avulsed and the track is closed. Delay in removal of suture may lead to complications. Healing by second intention (secondary union) This happens in wounds which are Open with large tissue defect, may be infected Having more loss of tissues and cells Wound is not approximated by surgical sutures Stages of secondary healing: 1. Initial haemorrhage 2. Inflammatory phase 3. Epithelial changes: epithelial cells proliferate from the edges and close the defect but this takes more time as the area to be closed is large and the epithelium does not fully cover the wound till granulation tissue fills up the defect from below. Healing by second intention (secondary union) 4. Granulation tissue: main bulk of the secondary healing is by formation of the granulation tissue. It is named so because of the granular and pink appearance of the tissue. Each granule corresponds to proliferation of a new blood vessel. Formation of granulation tissue involves proliferation of new blood vessels (angiogenesis or neovascularisation), the new vessels when they are newly formed are leaky but later become more stable. The second important process taking place is formation of new fibers (fibrogenesis), the newly formed blood vessels are seen in an amorphous ground substance, which starts to get filled up by collagen fibers (6th day). This changes the colour of the wound from red to pale pink. Healing by second intention (secondary union) 5. Wound contraction: an important feature of this type of healing. Starts after 2-3 days and continues till the 14th day. During this time the wound is reduced in size. this helps in rapid healing as the area of the injured tissue which has to be replaced is less. wound contraction takes place during granulation tissue formation. Complications of wound healing 1. Infection –delays wound healing 2. Implantation 3. Pigmentation 4. Deficient scar formation 5. Incisional hernia 6. Hypertrophied scars and Keloid formation 7. Excessive contraction 8. Neoplasia HEALING OF BONES – FRACTURE HEALING Bone fractures also heal by either primary union or secondary union. Primary union: occurs when there is approximation of fractured ends by application of compression clamps. Healing takes place by formation of medullary callus without formation of periosteal callus. Secondary union: this is the more common process. Involves three main stages 1. Procallus formation 2. Osseous callus formation 3. Remodelling HEALING OF BONES – FRACTURE HEALING 1. Procallus formation: the first step is haematoma formation, which occurs due to bleeding from torn vessels. This is followed by inflammatory response. Proliferation of mesenchymal cells from the periosteum and endosteum leads to formation of granulation tissue. this is known as soft tissue callus – it joins the two ends of the fractured bone. Woven bone and cartilage start growing in this granulation tissue. A wider zone of the fractured bone is covered by woven bone and cartilage, this helps in immobilising the fractured bone ends. This stage is known as procallus formation and is divided into external procallus, intermediate procallus and internal procallus. HEALING OF BONES – FRACTURE HEALING 2. Osseus callus formation: The procallus is invaded by new blood vessels and ostoblasts, which replace the woven bone and cartilage with lamellar bone. 3. Remodelling: in this stage both osteoblastic and osteoclastic activity is taking place. The external callus is cleared away, compact bone is formed in place of intermediate callus and bone marrow cavity develops in place of internal callus.