KAAF University College Pathology Lecture 4 PDF

KAAF UNIVERSITY COLLEGE SCHOOL OF NURSING/MW/PHN PATHOLOGY Lecture 4 LECT. RICHMOND KWAKYE Healing Of Wounds, Fractures And Special Tissues The word healing, used in a pathological context, refers to the body’s replacement of destroyed tissue by living tissue. ...

KAAF UNIVERSITY COLLEGE SCHOOL OF NURSING/MW/PHN PATHOLOGY Lecture 4 LECT. RICHMOND KWAKYE Healing Of Wounds, Fractures And Special Tissues The word healing, used in a pathological context, refers to the body’s replacement of destroyed tissue by living tissue.  Wound Healing A wound is a breach or defect in the structure of intact living tissue precipitated by injury and accompanied by inflammatory response. Whatever causes tissue injury may result in a wound and there will be accompanying inflammation A wound can be accidental or surgical  Types of Wounds Closed Wound: The surface of the skin is intact, but the underlying tissues may be damaged. e.g. contusions, haematomas, or Stage 1 Pressure Ulcers Open Wounds: the skin is split or cracked and the underlying tissues are exposed to the outside environment  Processes of wound healing The healing process involves two distinct processes: Regeneration: the replacement of lost tissue by tissues similar in type and Repair (healing by scaring), the replacement of lost tissue by granulation tissue which matures to form scar tissue.  Whether healing takes place by regeneration or by repair (scarring) is determined partly by the type of cells in the damaged organ & partly by the destruction or the intactness of the stromal frame work of the organ. Hence, it is important to know the types of cells in the body.  Types of cells Based on their proliferative capacity there are three types of cells. 1. Labile cells They are found in the surface epithelium of the gastrointestinal treat, urinary tract or the skin. The cells of lymphoid and haemopoietic systems are further examples of labile cells. The chances of regeneration are excellent 2. Stable cells Tissues which have such type of cells have normally a much lower level of replication and there are few stem cells. However, the cells of such tissues can undergo rapid division in response to injury. For example, mesenchymal cells such as smooth muscle cells, fibroblasts, osteoblasts and endothelial cells are stable cells which can proliferate. Liver, endocrine glands and renal tubular epithelium has also such type of cells which can regenerate. Their chances of regeneration are good. 3. Permanent cells These are non-dividing cells. If lost, permanent cells cannot be replaced, because they do not have the capacity to proliferate. For example: adult neurons, striated muscle cells, and cells of the lens.  objectives of wound healing 1. Restoration of an intact epithelial surface 2. Restoration of tensile strength of the sub- epithelial tissue Wound healing is a complex and orderly systematic process. It involves seven processes. 1. Acute inflammatory response upon injury 2. Regeneration of native cells of tissue involved. 3. Proliferation and migration of both native and connective tissue cells 4. Synthesis of extracellular matrix (ECM) proteins 5. Remodelling of connective tissue and parenchymal components 6. Collagenization and progressive acquisition of wound strength 7. Contraction.  Growth Factors Healing involves an orderly sequence of events which includes regeneration and migration of specialized cells, angiogenesis, proliferation of fibroblasts and related cells, matrix protein synthesis and finally cessation of these processes. These processes, at least in part, are mediated by a series of low molecular weight polypeptides referred to as growth factors. These growth factors have the capacity to stimulate cell division and proliferation. Some of the factors, known to play a role in the healing process  Sources of Growth Factors: Following injury, growth factors may be derived from a number of sources such as: 1. Platelets, activated after endothelial damage, 2. Circulating serum growth factors, 3. Macrophages, or 4. Lymphocytes recruited to the area of injury. The healing process ceases when lost tissue has been replaced  Healing by regeneration Definition: Regeneration (generare=bring to life) is the renewal of a lost tissue in which the lost cells are replaced by identical ones. Regeneration involves two processes 1. Proliferation of surviving cells to replace lost tissue 2. Migration of surviving cells into the vacant space. The capacity of a tissue for regeneration depends on its 1) proliferative ability, 2) degree of damage to stromal framework 3) the type and severity of the damage.  Wound contraction Wound contraction is a mechanical reduction in the size of the defect. The wound is reduced approximately by 70-80% of its original size. Contraction results in much faster healing, since only one-quarter to one-third of the amount of destroyed tissue has to be replaced. If contraction is prevented, healing is slow and a large ugly scar is formed. Causes of contraction Contraction by myofibroblasts. Myofibroblasts have the features intermediate between those of fibroblasts and smooth muscle cells. Two to three days after the injury they migrate into the wound and their active contraction decrease the size of the  Patterns Of Wound There are two patterns of wound healing depending on the amount of tissue damage: 1. Healing by first intention (Primary union) 2. Healing by second intention  Healing By First Intention Or Primary Union Healing by first intention or primary union is the means by which clean uninfected surgical wounds well approximated by sutures heal. Such surgical incisions cause death of minimal epithelial cells, connective tissue cells and minimal disruption of the basement membrane. Immediately after creating the wound, the body moves to fill the narrow incision space with clotted blood composed of fibrin and blood cells. This undergoes dehydration to form a scab. Process of primary union Within the first 24hrs (first day) Neutrophil invade the site of incision and move toward the fibrin clot. Proliferation of basal cells commence resulting in the thickening of the epidermis. 24-48hrs (1-2days) Epithelial cells accumulate at the margins of the dermis and deposit basement membrane components as they move along. The cells fuse in the midline beneath the scab to produce a thin but continuous epithelial layer.  By the third day Macrophage replace neutrophils. Granulation tissue invades the incision space Collagen fibres appear at the margins with a vertical orientation but do not bridge the incision. Epithelial cell proliferation continues so that the covering epidermis gets further thickened.  Fifth day Granulation tissue fills the incision space Proliferation of blood vessels and blood supply is optimal Further proliferation of collagen fibrils and bridging of the incision Normal epidermal thickness becomes restored Surface cells differentiate to achieve mature epidermal architecture with surface keratinization.  Two weeks Continued accumulation of collagen Proliferating of fibroblasts Decrease in leucocytic infiltrate Resorption of edema Regression of vascular channels Reduction in vascularity Increase in the deposition of collagen  One month Prominent scar tissue formation. Scar tissue is a dense and cellular connective tissue with intact epidermal covering. Absence of inflammatory infiltrate. Consequences Dermal and epidermal appendages are lost Tensile strength may take months to recover.  HEALING BY SECOND INTENTION Wounds with extensive loss of cells, large tissue defect and wide margins heal by second intention. This includes infarction, inflammatory ulceration and abscesses formation with large surface wounds. Implications of a large defect include: 1. Regeneration of native cells cannot suffice to close the large defect 2. Therefore abundant granulation tissue is needed. 3. Fibrin is more abundant. 4. There is more necrotic debris and exudates. 5. Intense inflammatory reaction is needed to remove the fibrin and necrotic debris. 6. Wound contraction by myofibroblasts.  Granulation tissue is a new connective tissue with microscopic blood vessels and myofibroblasts that develop at the wound site in the process of healing. It grows from the base of the wound and helps in filling the wounds. It is important for the contraction of the wound and epithelial cell migration.  Factors that influence wound healing A number of factors can alter the rate and efficiency of healing. Most of these factors have been established in studies of skin wound healing but many are likely to be of relevance to healing at other sites. Local Factors Systemic factors  Local Factors Type, size, and location of the wound A clean, aseptic wound produced by the surgeon’s scalpel heals faster than a wound produced by blunt trauma, which exhibits abundant necrosis and irregular edges. Small blunt wounds heal faster than larger ones. Injuries in richly vascularized areas (e.g., the face) heal faster than those in poorly vascularized ones (e.g., the foot). In areas where the skin adheres to bony surfaces, as in injuries over the tibia, wound contraction and adequate apposition of the edges are difficult. Hence, such wounds heal slowly.  Vascular supply Wounds with impaired blood supply heal slowly. For example, the healing of leg wounds in patients with varicose veins is prolonged. Ischemia(less than normal amount of blood flow) due to pressure produces bed sores and then prevents their healing. Ischemia due to arterial obstruction, often in the lower extremities of diabetics, also prevents healing.  Infection Wounds provide a portal of entry for microorganisms. Infection delays or prevents healing, promotes the formation of excessive granulation tissue (proud flesh), and may result in large, deforming scars.  Movement Early motion, particularly before tensile strength has been established, subjects a wound to persistent trauma, thus preventing or retarding healing. Ionizing radiation Prior irradiation leaves vascular lesions that interfere with blood supply and result in slow wound healing. Acutely, irradiation of a wound blocks cell proliferation, inhibits contraction, and retards the formation of granulation tissue.  Systemic Factors Circulatory status Cardiovascular status, by determining the blood supply to the injured area, is important for wound healing. Poor healing attributed to old age is often due, largely, to impaired circulation. Infection Systemic infections delay wound healing.  Metabolic status Poorly controlled diabetes mellitus is associated with delayed wound healing. The risk of infection in clean wound approaches five fold the risk in non- diabetics. In diabetic patients, there can be impaired circulation secondary to arteriosclerosis and impaired sensation due to diabetic neuropathy. The impaired sensation renders the lower extremity blind to every day hazards. Hence, in diabetic patients, wounds heal the very slowly.  Nutritional deficiencies Protein deficiency Vitamin deficiency Trace element deficiency Anti-inflammatory drugs Anti-inflammatory medications do not interfere with wound healing when administered at the usual daily dosages. Aspirin and indomethacin both inhibit prostaglandin synthesis and thus delay healing.  Complications of Wound Healing Abnormalities in any of the three basic healing processes – contraction, repair, and regeneration – result in the complications of wound healing. 1. Infection A wound may provide the portal of entry for many organisms. Infectrion may delay healing, and if severe stop it completely. 2. Deficient Scar Formation Inadequate formation of granulation tissue or an inability to form a suitable extracellular matrix leads to deficient scar formation and its complications. The complications of deficient scar formation are: a. Wound dehiscence & incitional hernias b. Ulceration  Wound Dehiscence and Incisional Hernias: Inappropriate suture material and poor surgical techniques are important factors. Wound infection, increased mechanical stress on the wound from vomiting, coughing, or ileus is a factor in most cases of abdominal dehiscence An incisional hernia, usually of the abdominal wall, refers to a defect caused by poor wound healing following surgery into which the intestines protrude Incisional Hernias  Ulceration: Wounds ulcerate because of an inadequate intrinsic blood supply or insufficient vascularization during healing. For example, leg wounds in persons with varicose veins or severe atherosclerosis typically ulcerate. Non-healing wounds also develop in areas devoid of sensation because of persistent trauma. Such trophic or neuropathic ulcers are occasionally seen in patients with leprosy, diabetic peripheral neuropathy and in tertiary syphilis from spinal involvement. 3. Excessive Scar Formation An excessive deposition of extracellular matrix at the wound site results in a hypertrophic scar or a keloid. The rate of collagen synthesis, the ratio of type III to type I collagen, and the number of reducible cross-links remain high, a situation that indicates a “maturation arrest”, or block, in the healing process Contractures result from excessive contractions in some sites such as the palm, soles and anterior aspect of the thorax. This is commonly seen in post burns healing  Steps Involved in Wound Healing. Formation of Blood Clot. Wounding causes the rapid activation of coagulation pathways, which results in the formation of a blood clot on the wound surface. In addition to entrapped red cells, the clot contains fibrin, fibronectin, and complement components. The clot serves to stop bleeding and also as a scaffold for migrating cells, which are attracted by growth factors, cytokines and chemokines released into the area.  Formation of Granulation Tissue. Fibroblasts and vascular endothelial cells proliferate in the first 24 to 72 hours of the repair process to form a specialized type of tissue called granulation tissue, which is a hallmark of tissue repair. Granulation tissue progressively invades the incision space; the amount of granulation tissue that is formed depends on the size of the tissue deficit created by the wound and the intensity of inflammation. Hence, it is much more prominent in healing by secondary union. By 5 to 7 days, granulation tissue fills the wound area and neovascularization is maximal  Cell Proliferation and Collagen Deposition. Neutrophils are largely replaced by macrophages by 48 to 96 hours. Macrophages are key cellular constituents of tissue repair, clearing extracellular debris, fibrin, and other foreign material at the site of repair, and promoting angiogenesis and ECM deposition Scar Formation. The leukocytic infiltrate, edema, and increase vascularity largely disappear during the second week. Blanching begins, accomplished by the increased accumulation of collagen within the wound area and regression of vascular channels. Ultimately, the original granulation tissue scaffolding is converted into a pale, avascular scar, composed of spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components  Wound Contraction. Wound contraction generally occurs in large surface wounds. The contraction helps to close the wound by decreasing the gap between its dermal edges and by reducing the wound surface area. Hence, it is an important feature in healing by secondary union.  Fracture Healing Unlike healing of a skin wound, however, the defect caused by a fracture is repaired not by a fibrous “scar” tissue, but by specialized bone forming tissue so that, under favorable circumstances, the bone is restored nearly to normal.  Structure of bone Bone is composed of calcified osteoid tissue, which consists of collagen fibers embedded in a mucoprotein matrix (osteomucin). Depending on the arrangement of the collagen fibers, there are two histological types of bone: 1. Woven, immature or non-lamellar bone. This shows irregularity in the arrangement of the collagen bundles and in the distribution of the osteocytes. The osseomucin( binds collagen and elastic fibrils) is less abundant and it also contains less calcium. 2. Lamellar or adult bone In this type of bone, the collagen bundles are arranged in parallel sheets.  Stages in Fracture Healing (Bone Regeneration) Stage 1: Haematoma formation. Immediately following the injury, there is a variable amount of bleeding from torn vessels; if the periosteum is torn, this blood may extend into the surrounding muscles. If it is subsequently organized and ossified, myositis ossificans( rxn to bruises , calcium formed to harden) results. Stage 2: Inflammation. The tissue damage excites an inflammatory response, the exudate adding more fibrin to the clot already present. There is an increased blood flow and a polymorphonuclear leucocytic infiltration.  Stage 3: Demolition. Macrophages invade the clot and remove the fibrin, red cells, the inflammatory exudate, and debris. Any fragments of bone, which have become detached from their blood supply, undergo necrosis, and are attacked by macrophages and osteoclasts. Stage 4: Formation of granulation tissue. Following this phase of demolition, there is an ingrowth of capillary loops and mesenchymal cells derived from the periosteum and the endosteum of the cancellous bone. These cells have osteogenic potential and together with the newly formed blood vessels contribute to the granulation –tissue formation.  Stage 5: Woven bone and cartilage formation. The mesenchymal “osteoblasts” next differentiate to form either woven bone or cartilage. The term “callus”, derived from the Latin and meaning hard, is often used to describe the material uniting the fracture ends regardless of its consistency. When this is granulation tissue, the “callus” is soft, but as bone or cartilage formation occurs, it becomes hard.  Stage 6: Formation of lamellar bone. The dead calcified cartilage or woven bone is next invaded by capillaries headed by osteoclasts. As the initial scaffolding (“provisional callus”) is removed, osteoblasts lay down osteoid, which calcifies to form bone. Its collagen bundles are now arranged in orderly lamellar fashion, for the most part concentrically around the blood vessels, and in this way the Haversian systems are formed. Adjacent to the periosteum and endosteum the lamellae are parallel to the surface as in the normal bone. This phase of formation of definitive lamellar bone merges with the last stage.  Stage 7: Remodelling. The final remodeling process involving the continued osteoclastic removal and osteoblastic laying down of bone results in the formation of a bone, which differs remarkably little from the original tissue. The external callus is slowly removed, the intermediate callus becomes converted into compact bone containing Haversian systems, while the internal callus is hollowed out into a marrow cavity in which only a few spicules of cancellous bone remain. Fracture healing