PTY Unit 5: Tissue Repair PDF

1 OBJECTIVES: - DESCRIBE THE COMPONENTS OF THE HEALING PROCESS IN DAMAGED TISSUE - EXPLAIN THE STAGES ON WHICH HEALING TAKES PLACE - IDENTIFY THE FACTORS THAT INFLUENCE HEALING - INDICATE THE PO...

1 OBJECTIVES: - DESCRIBE THE COMPONENTS OF THE HEALING PROCESS IN DAMAGED TISSUE - EXPLAIN THE STAGES ON WHICH HEALING TAKES PLACE - IDENTIFY THE FACTORS THAT INFLUENCE HEALING - INDICATE THE POSSIBLE COMPLICATIONS OF THE HEALING PROCESS OVERVIEW This prompts the body’s natural processes to restore tissue continuity -> thus leading to the development of healing/repair TERMINOLOGY ❖ Cell proliferation = process of increasing cell numbers by mitotic division ❖ Cell differentiation =process whereby a cell becomes more specialized in terms of structure + function ❖ Stem cells = undifferentiated cells that have the capacity to generate into multiple cell types -> most commonly produced in bone marrow ❖ Cell cycle = orderly sequence of events in which the cell duplicates its genetic contents + divides NOTES BY GABRIELLA ADOLPHE  2 TISSUE REPAIR: REGENERATION, HEALING, FIBROSIS – VIDEO NOTES Scenario: You have a liver (liver cells = hepatocytes) -> for some reason there is a problem where the cells are deleted -> liver necrosis happens -> this liver is now missing a part of itself The cells on the border of the deleted cells/missing part, will initiate a cascade of tissue repair, if they are able to divide they will go through the cell process of division and try to regrow the architecture of this organ = REGENERATION If the cells cannot divide (regenerate), Healing + fibrosis occurs (usually work together) o HEALING – fibroblasts will be recruited to the area and lay down a mass of collagen + scar tissue -> to try to maintain the architecture of the organ, but you lose some function o When fibrosis happens you the lose function of the area, but in regeneration, the function and shape almost are maintained. TISSUE REPAIR Repair (healing) refers to the restoration of tissue architecture + function after an injury Note: By convention, Repair for -> Parenchymal + connective tissues & Healing for -> surface epithelia ❖ The ability to repair damage, toxic insults + inflammation = critical to the survival of an Organism ❖ Inflammatory response to microbes + injured tissues -> not only serves to eliminate these dangers but also sets into motion the process of repair ❖ Repair of damaged tissues occurs by 2 types of reactions: 1. Regeneration by proliferation [increased cell numbers by mitosis] of residual (uninjured cells) -> driven by growth factors ▪ Cells types that proliferate: remnants of injured parenchymal, vascular endothelial cells + fibroblasts 2. Maturation of tissue stem cells ❖ Deposition of connective tissue = Scar ❖ The inflammatory response 1. Regeneration 2. Healing 3. Fibrosis THE 4 STEP PROCESS OVERVIEW OF TISSUE REPAIR – VIDEO NOTES INJURY REPAIR BY NEW CONNECTIVE TISSUE REPLACEMENT Scenario: Finger is sliced during cooking, and blood is coming out. Tissues cut through: fingernail, epithelial [skin] , through the muscle tissue, cut through nerve endings Nerve cells don’t divide, skin cells divide a lot Within in 24hrs -> inflammation process, leukocytes will start coming to the area, fibroblasts will come to the area & lay down collagen + components that will form scar connective tissue -> they will start repair 3-5 Days -> a new scar tissue formed to fill in place of nerve + new skin tissue -> granulation tissue (pinkish tissue) [normally around scab] NOTES BY GABRIELLA ADOLPHE  3 4 STEPS: 1. Formation of new blood vessels (angiogenesis) 2. Migration + proliferation [mitotic division] of fibroblast -> to increase the number of “workers” 3. Deposition of ECM [extra-cellular matrix] (scar tissue) 4. Maturation + reorganisation [in order to try gain function] of the fibrous tissue (remodelling) COMPONENTS OF THE HEALING PROCESS ❖ Resolution = takes place when the injured tissue is restored to its pre-injury state ❖ Regeneration = replacement of injured tissue from parenchyma ❖ Repair/healing = when fibrous scar tissue fills the gap ❖ Revascularisation = newly formed tissue needs a blood supply, thus revascularisation is an important aspect of healing ❖ Reepithelialisation = injury often involves internal or external body surfaces + therefore the protective epithelium needs to be restored. NB: Organs are composed of Parenchyma (functional cells) that are bound together by stroma (supporting connective tissue, blood vessels, fibroblasts, nerve fibers + extracellular matrix) REGENERATION Proliferation [mitotic division] of parenchymal cells Cells lost through injury may be replaced by cell division (mitosis) of health adjacent parenchymal cells Process continues until the volume of the new tissue is more or less the same as the volume of the tissue that was lost through injury Shape (architecture) + function mainted E.g. the epithelia of the skin + intestine & in some parenchymal organs e.g. the liver CELL CAPACITY FOR REGENERATION: The ability of cells to repair themselves is determined by their intrinsic [effects originate from inside of an organism/cell] proliferative capacity -> their ability to regenerate Based on this, cells are÷ divided into 3 groups: 1. Labile Cells (continuously dividing) e.g. epithelial cells of the skin 2. Stable Cells 3. Permanent cells NOTES BY GABRIELLA ADOLPHE  4 1. Labile Cells (continuously dividing) Labile (continuously dividing) tissues. Cells of these tissues are continuously being lost and replaced by maturation from tissue stem cells and by proliferation. [increased cell numbers by mitotic division] Labile cells include: o Hematopoietic cells in the bone marrow o The majority of surface epithelia o Stratified squamous epithelia of the skin, oral cavity, vagina, cervix; the cuboidal epithelia of the ducts draining exocrine organs (e.g. salivary glands, pancreas, biliary tract); the columnar epithelium of the gastrointestinal tract, uterus, and fallopian tubes; and the transitional epithelium of the urinary tract -> these tissues can readily regenerate after injury as long as the pool of stem cells is preserved. 2. Stable Cells Cells of these tissues are quiescent [in a state of inactivity/dormancy] (in the G0 stage of the cell cycle) + have only minimal proliferative activity in their normal state. -> normally stop dividing when growth ceases Are capable of dividing in response to injury or loss of tissue mass (an appropriate stimulus) Constitute the parenchyma of most solid tissues -> liver, kidney, pancreas Also include endothelial cells, fibroblasts + smooth muscle cells -> the proliferation of these cells is particularly important to wound healing With the exception of the liver, stable tissues have a limited capacity to regenerate after injury. 3. Permanent Cells Considered to be terminally differentiated [once acquired a specialised function, has irreversibly lost its ability to proliferate] + non-proliferative in postnatal life Permanent cells -> majority of neurons + cardiac muscles Thus Injury to the brain/heart is irreversible + results in a scar -> neurons and cardiac myocytes cannot regenerate Limited stem cell replication + differentiation occur in some areas of the adult brain -> there is some evidence that heart muscle cells may proliferate after myocardial necrosis Whatever proliferative capacity may exist in these tissues, it is insufficient to produce tissue regeneration after injury. Skeletal muscle = permanent tissue -> but satellite cells attached to the endomysial sheath [connective tissue layer that surrounds a each single muscle fiber] provide some regenerative capacity for muscle Permanent tissues = repair dominated by scar formation NOTES BY GABRIELLA ADOLPHE  5 SUMMARY LABILE CELLS STABLE CELLS PERMANENT CELLS Cells + proliferation *Cells replaced by *Minimally *Terminally mature stem cells proliferative differentiated + non- and proliferation proliferative in postnatal life Regeneration *Yes, as long as the *do not divide but *Unable to pool of stem cells is are capable of regenerate kept alive regeneration when *Repair dominated by confronted with an scar formation. appropriate stimulus *Insufficient to *Limited capacity to reproduce tissue regenerate after regeneration after injury injury HEALING BY CONNECTIVE TISSUE REPAIR Tissue loss replaced with granulation tissue + fibrous repair takes place Phases of repair 1. Haemostasis [process to prevent + stop bleeding], Angiogenesis [formation of new blood vessels] + ingrowth of granulation tissue [composed of fibroblasts, loose connective tissue, vessels, leukocytes] 2. Emigration of fibroblasts + deposition of extracellular matrix. 3. Maturation + reorganization of the fibrous tissue (remodelling) Process Occurs: when injured tissue is incapable of complete restitution OR supporting structures are severely injured Thus there is a laying down of fibrous connective tissue to restore the strength + structure of tissue Fibroblasts (specialised cells) -> lay down strong, collagen-rich tissue to form a scar (fibrosis) Fibrosis = scar formation is a response that “patches” rather than restores the tissue NB: Fibrous strands can become organized within the peritoneal cavity [space between the peritoneum that surrounds the abdominal wall and the peritoneum that surrounds the internal organs] following surgery or peritonitis [inflammation of the peritoneum]. These strands are called adhesions + can trap loops of bowel causing obstruction Revascularization NOTES BY GABRIELLA ADOLPHE  6 Revascularization (angiogenesis) = restoration of blood circulation of an organ/area Newly formed tissue ->requires a blood supply, therefore revascularization is an important aspect of repair This process is controlled by chemical signals in the body -> involves the migration, growth + differentiation of endothelial cells -> which line the inside wall of blood vessels Several growth factors induce angiogenesis -> most important growth factor = VEGF (vascular endothelial growth factor) -> signalling protein that promotes the growth of new blood vessels Re-epithelization Re-epithelization = the replacement of the lost surface lining by mitosis of epithelial cells Injury often involves internal/external body surfaces -> therefore the protective epithelium needs to be restored The formation of granulation tissue into an open wound -> allows the re-epithelialisation phase to take place Epithelial cells migrate across the new tissue to form a barrier between the wound and the environment -> epithelial migration continues until cells from the opposite edge meet CUTANEOUS [relating to or affecting the skin] WOUND HEALING Involves epithelial cell regeneration + connective scar formation Depending on severity of tissue loss, healing occurs either by: o First (primary intention) e.g. sutured surgical wound o Second (secondary intention) e.g. burns, large surface wounds Cutaneous wound healing is divided into 3 phases: 1. Inflammatory (vascular + cellular stages) 2. Proliferative (2-3 days after injury -> new tissue to fill the wound space) 3. Remodelling (3 wks after injury – remodelling of scar tissue) NB: Duration of phases depends on extent of the injury THE INFLAMMATORY PHASE (1st 24 hrs) Begins @ time of injury, with formation of a blood clot + the migration of phagocytic white blood cells into the wound site Neutrophils -> ingest + remove bacteria and cellular debris After 24hrs, neutrophils joined by Macrophages -> which continue to ingest cellular debris + play an essential role in the production of growth factors for the proliferative phase NOTES BY GABRIELLA ADOLPHE  7 PROLIFERATIVE PHASE (3-7 days) The primary focus -> building of new tissue to fill wound space Key cell during this phase = fibroblast; connective tissue cell that synthesizes collagen and proteins needed for wound healing + produces growth factors that induce angiogenesis, endothelial cell proliferation + migration Final component of proliferative phase -> epithelialization – epithelial cells at the wound edges proliferate to form a new surface layer WOUND CONTRACTION + REMODELLING PHASE (3 weeks) Begins after 3 wks with development of the fibrous scar, can continue for 6 months or longer There is a decrease in vascularity + continued remodeling of scar tissue by simultaneous synthesis of collagen by fibroblasts & lysis by collagen enzymes -> resulting in the architecture of the scar to have an increased tensile strength + scar shrinks (less visible) Healing by 1st intention (e.g. skin wound) Occurs: site where there is minimal loss of tissue e.g. surgical incision Actue inflammatory response is minimal The edges of a wound are held together by a thin film of clotted blood Proliferation of adjacent epithelial cells restore continuity at an early stage Macrophages -> remove debris + inactivate disease agents Fibroblasts -> migrate to the area + begin to form connective tissue fibres Where possible, health cells multiply to restore normal function + appearance NB: Look at picture + steps Picture 1: 24hrs Picture 2: 3-7 days Picture 3: 3 weeks NOTES BY GABRIELLA ADOLPHE  8 Healing by 2nd intention e.g. burns, ulcer, abscess cavity Occurs: when tissue loss is greater & edges of the wound are not close together Healing process takes longer -> more regeneration + repair is needed Infection or trauma has to be overcome by an acute inflammatory response and all debris removed by macrophages In trauma -> defect is filled by clotted blood Healing starts from the floor of the wound -> through the action of leukocytes (reticuloendothelial or white blood cells), histiocytes (macrophages), fibroblasts + re-vascularization New delicate connective tissue is formed -> called granulation tissue -> consisting of fibroblasts, collagen + capillaries Granulation tissue matures from the bottom up, until the area is filled with fibrous or scar tissue Surface epithelial cells at the periphery proliferate + cover the granulation tissue Contraction of the wound occurs -> resulting in a scar that is smaller than the original defect Initially the scar = red, but turns white -> as capillaries die away Summary of Wound Healing PRIMARY UNION (1ST SECONDARY UNION (2ND INTENTION) INTENTION) CLEANLINESS Clean Unclean INFECTION Generally Uninfected May Be Infected MARGINS Surgically Clean Irregular SUTURES Used Not Used HEALING Scanty [Small Amount] Exuberant [Large Amount] Granulation Tissue @ The Granulation To Fill The Gap Incised Gap + Along Suture Tracks OUTCOME Neat Linear Scar Contracted Irregular Scar COMPLICATIONS Infrequent, Epidermal Suppuration, May Require Inclusion Cyst Formation Debridement [Removal Of Dead/Damaged Tissue] ACUTE INFLAMMATORY Minimal Prominent RESPONSE EDGES OF WOUND Close Further Apart TIME Shorter Longer NOTES BY GABRIELLA ADOLPHE  9 How a bone heals after it has been fractured (video notes) Types of fractures: shattered (multiple pieces), liner fracture (down the shaft), displaced fracture (bone misaligned), oblique fracture (sloped pattern) Bone cells: o Osteoblasts (build up bone tissue) o Osteoclasts (break down bone tissue) o Chondroblasts (build up cartilage tissue) o Fibroblasts (produce collagen fibres) How to heal a simple bone fracture: 1. Swelling + Bleeding begins -> leads to a blood clot 2. Phagocytes (white blood cells) will come in and clean up the area -> by removing dead cells + germs that may have entered the area 3. As the blood clot reduces -> osteoclasts appear + take care of dead bone fragments 4. Chondroblasts form a fibrocartilaginous tissue -> which holds the broken ends together 5. At the same time, osteoblasts + fibroblasts work -> the fibrocartilaginous tissue is called a soft callus, this then hardens into a bony callus 6. Usually results in excessive bone tissue -> thus osteoclasts reabsorb some of the extra tissue 7. After this process, the bone will not be 100% & a slight bump may remain @ spot of the break Some things may impair proper healing: Poor blood supply Poor general heath Infections Age (younger bones heal faster) Type of break FACTORS THAT INFLUENCE TISSUE REPAIR Infection/presence of foreign material (bacterial contamination) o Infection impairs all dimensions of healing o Prolongs the inflammatory process, impairs the function of granulation tissue, inhibits proliferation of fibroblasts + deposition of collagen fibers o Although body defenses can handle the invasion of microorganism @ at the time of wounding, badly contaminated wounds can overwhelm host defenses -> leading to infection (foreign bodies tend to invite bacterial contamination + delay healing) o Sutures = foreign body; this is why sutures are removed as soon as possible after surgery o Wound infections concern with patients with implantation of foreign bodies e.g. orthopedic devices, cardiac pacemakers, shunt catheters -> difficult to treat + may require removal NOTES BY GABRIELLA ADOLPHE  10 Diabetes o Poor wound healing + poor collagen formation, particularly in those who have poorly controlled blood glucose levels o The effect of hyperglycemia [high blood sugar] on phagocytic function e.g. neutrophils have diminished chemotactic and phagocytic function (engulfment + intracellular killing of bacteria) when exposed to altered glucose levels o Small blood vessel disease also common in those with diabetes -> impairing delivery of inflammatory cells, oxygen, nutrients to wound site Nutritional status (lack of vitamins) o Successful wound healing depends partly on adequate stores of proteins, carbohydrates, fats, vitamins + minerals. Malnutrition slows the healing process, causing wounds to heal inadequately or incompletely. Corticosteroids o Therapeutic administration of corticosteroid drugs [steroids – anti-inflammatory drug] may delay the healing process o These hormones decrease capillary permeability during the early stages of inflammation, impair the phagocytic property of leukocytes + inhibit fibroblast proliferation & function Mechanical (increase pressure or torsion) o Mechanical factors such as increased local pressure/torsion can cause wounds to pull apart (dehisce) causing wounds to take longer to heal as the epithelization process needs to begin again o Increased pressure can also disrupt blood flow, impairing wound healing Poor perfusion (vascularity) -> leads to poor blood circulation (lack of oxygen) o oxygen is a requirement for various processes in the healing of wounds including collagen deposition, epithelization, fibroplasia, angiogenesis, and resistance to infection o For healing to occur, wounds must have adequate blood flow to supply the necessary nutrients + to remove the resulting waste, local toxins, bacteria & other debris o Oxygen is required for collagen synthesis + killing of bacteria by phagocytic blood cells o Neutrophils + macrophages require oxygen for destruction of microorganism that have invaded the area. o Low blood pressure/vascular disease, narrowed, blocked blood vessels can cause issues in the delivery of essential components for wound healing The type + extent of the injury o Approximation of wound edges (i.e. suturing) greatly enhances healing + prevents infection o epithelialization of a wound with closely approximated edges occurs within 1-2 days; gaping wounds tend to heal more slowly because it is virtually impossible to effect wound closure o Larger wounds that have a greater loss of tissue heal by secondary intention -> unpredictable -> results in larger amounts of scar tissue o Shape -> liner wounds are quicker to heal, rectangular/circular wounds slower to heal NOTES BY GABRIELLA ADOLPHE  11 Location of the injury o Wounds heal slowly and may not heal at all in an environment in which they are repeatedly traumatised or deprived of local blood supply Age (decline in collagen synthesis + reduced rate of proliferation) o Structural + functional changes occur in aging skin -> decrease in dermal thickness, decline in collagen concentration, loss of elastiscity o Elderly have alterations in wound-healing phases including hemostasis, inflammation, cell proliferation -> vascular endothelial cells display a reduced rate in proliferation o Decrease in angiogenesis [formation of new blood vessels], collagen synthesis, impaired wound contraction + slower re-epithelialization of open wounds COMPLICATIONS OF THE REPAIR PROCESS Infection Inadequate formation of granulation tissue (thus resulting in wound dehiscence + ulceration) Excessive contraction of a scar (resulting in a skin deformity, obstruction of hollow organ such as the oesophagus + contraction of the scarred heart valves resulting in stenosis (narrowing) Hypertrophic scar [a thickened, raised scar] or keloid formation Pain (due to formation of a neuroma) Weakness (fibrous scar tissue has less strength) Cancer (developed from a chronic scarred ulcer) NB: for test purposes, you need to be able to elaborate on the complications + factors the influence the repair process NOTES BY GABRIELLA ADOLPHE