Repair

Repair and healing Dr. Mehzabin Ahmed

Outcomes of inflammation

Tissue repair 

Two separate processes underlie the repair of tissue damage ( caused by surgical resection, wounds, chronic inflammation etc.): 

1.Regeneration – (replacement of injured cells by cells of same type) results in restitution of lost tissues, requires an intact connective tissue scaffold.

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2.Healing- may restore original structures but involves scar formation; occurs when the extracellular matrix (ECM) frame work is damaged; as well as in permanent tissues following tissue necrosis.

Tissue proliferative activity Tissues of the body are divided into 3 groups based on their proliferative capacity 

Labile tissues ("continuously dividing tissues") are constantly replenishing their neighbors which have died or been shed. Examples include the epithelium of skin, mucous membranes, oviducts, ducts; urothelium; endometrium; seminiferous tubules; bone marrow; in most of these tissues , mature cells are derived from stem cells. 

Epidermis can regenerate from the skin adnexal structures (hair follicles, sebaceous glands, sweat glands), enabling full removal of epidermis as for a skin graft.

Tissue proliferative activity (contd.) 

Quiescent or Stable tissues ("discontinuous replicators") can proliferate rapidly in response to need, especially when required to replace lost neighbors. These include all glandular parenchymal cells, endothelial cells as well as mesenchymal cells such as fibroblasts,smooth muscle cells,chondrocytes, and osteoblasts. 

The best example of regenerative capacity of stable cells is the regeneration of liver after partial hepatectomy.

Tissue proliferative activity (contd.) 

Non dividing (permanent) tissues contain cells that have left the cell cycle cannot undergo mitosis or be replenished after birth. These cells include neurons, cardiac and skeletal muscle cells.

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Obviously, cells will not regenerate if there is inadequate blood supply, inadequate nutrition, or complete destruction of their connective tissue framework.

Cell populations and cell cycle phases

Tissue response to injury: repair after injury can occur by regeneration which restores normal tissue or by healing which leads to scar formation Normal homeostasis Balance of proliferation and apoptosis

injury Regeneration

Healing Permanent tissues

Renewing tissues

Stable tissues inflammation

fibrosis Epidermis, GIT, Hemopoeitic

Compensatory growth of Liver and kidney

Wound healing Scar formation

Resolution 

Occurs when there has been minimal damage to tissue architecture and the cells can regenerate. 

E.g.:Lobar pneumonia, under favourable conditions, the injured area returns to its normal structure and function  The

inflammatory exudate is removed by liquefaction

and phagocytosis, damaged cells regenerate and repopulate the injured alveoli

Healing by collagenous scar

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Organization is the process by which inflammatory exudate is replaced by granulation tissue

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The process by which granulation tissue is subsequently replaced by fibrous scar is called fibrous repair

Healing by collagenous scar (contd.) 

1.Organization and repair following acute inflammation; e.g. severe structural damage to the supporting stroma as in an abscess, fibrinous exudates on serosal surfaces, necrosis in tissues containing permanent cells and

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2.Chronic inflammation eventually heals by scarring

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3. Healing of wounds (Tissue wounds including surgical wounds)

inflammatory processes in body cavities may result in the formation of adhesions, which are thin bands of collagenous connective tissue, as seen here between the right lung and the chest wall at autopsy. Adhesions, if extensive can restrict motion or cause retraction to an abnormal position of internal organs.

The best possible outcome following an inflammatory process is complete resolution, leaving the tissues intact and undamaged. However, chronic inflammation may occur in conjunction with some degree of scarring. Here, chronic inflammation of the bronchi has led to dilation and scarring with increased tan to white collagenous tissue.

Sequence of changes in healing 

Replacement of area of tissue damage by vascular granulation tissue

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Progressive growth of fibroblasts in the granulation tissue ( fibrovascular granulation tissue)

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Progressive collagen synthesis and deposition in the granulation tissue( fibrous granulation tissue),contraction of area through the effects of myofibroblasts

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Production of dense collagen – collagenous scar

Healing of Tissue wounds (including surgical wounds)   

Achieved by organization, repair and scar formation Healing by Primary intention : healing of closely apposed surfaces as in a clean sutured surgical wound Healing by secondary intention: healing of open wounds  Differences between the two relate to the amount of granulation tissue required to fill the tissue defect  Wound contraction – the process by which the surface area of an open wound is reduced to about 10% of its original size; characteristic of healing by secondary intention , caused by contraction of myofibroblasts.

HEALING BY SECOND INTENTION WOUNDS WITH SEPARATED EDGES)

Steps in wound healing by first intention (left) and second intention (right). Secondary healing differs from primary healing in several respects:   

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inflammatory reaction is more intense. Much larger amounts of granulation tissue are formed. wound contraction, by myofibroblasts at the wound site decreases the gap between the dermal edges of the wound. Substantial scar formation and thinning of the epidermis.

Stages in the healing of a sutured skin wound 

Day 1 : acute inflammatory response at the margins of incision , epithelial cell regeneration begins

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Day 2: thin surface layer establishes epithelial continuity, Macrophages begin to appear

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Day 3: granulation tissue begins to invade tissue space, thickening of epithelial layer

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Day 5: vascular granulation tissue fills the incisional space, swelling and redness subsides

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Day 7: sutures commonly removed , wound has about 10% of tensile strength of the normal skin

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Day 10: fibrous granulation tissue,adds to wound strength

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Day 15: collagen deposition along the line of stress,pale pink in appearance

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Day 30: 50% tensile strength

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3 months: max. tensile strength of 80%, scar

This is a healing biopsy site on the skin seen a week following the excision, The skin surface has reepithelialized, and below this is granulation tissue with small capillaries and fibroblasts forming collagen. After a month, just a small collagenous scar will remain.

Cellular events in wound healing 

5 key events in healing by organization and repair: 

Local vessels:  1.angiogenesis

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Local support cells  2.

Divide to form fibroblasts and myofibroblasts (mitogenesis)

 3.migrate

towards the area of tissue damage (chemotaxis and motility )

 4.secrete  5.

collagen (fibrogenesis)

Produce collagen degrading enzymes ( remodeling)

Local and systemic factors influence healing 

Systemic factors: 

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Inadequate nutrition ( protein, vit.C and Zinc)

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Steroids

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Diabetes Mellitus

Local: 

Infection

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Foreign material

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Ischemia to tissues, radiation , denervation

This patient had diabetes mellitus for many years. This disease leads to marked atherosclerosis with arterial narrowing. When peripheral arteries to the legs are involved, then ischemia of soft tissues and bone occurs. Even minor trauma leads to ulceration that heals poorly and often becomes secondarily infected. A transmetatarsal amputation has already been performed in this patient because of the severity of peripheral vascular disease.

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Healing is promoted by: 

Removal of dead tissue to allow apposition of healthy tissues

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Administration of appropriate antibiotics in cases of infection

Healing in specialized tissues 

Damaged brain heals by growth of astrocytes and not by fibroblasts; necrotic tissue is removed and replaced by fluid,forming a cystic lesion,surrounded by glial tissue

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Repair of bone damage (fracture) : a fibrous scar is an inadequate end-result in bone healing; 

in addition to granulation tissue formation and fibrous repair, there is formation of a callus( mass of fibrous tissue,bone and cartilage, from which healed bone will arise),

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with remodeling of callus the normal structure of bone prior to fracture is re-established.

Myocardium: Healing by scar formation There has been a previous extensive transmural myocardial infarction involving the free wall of the left ventricle. Note that the thickness of the myocardial wall is normal superiorly, but inferiorly is only a thin fibrous wall. The infarction was so extensive that, after healing, the ventricular wall was replaced by a thin band of collagen, forming an aneurysm. Such an aneurysm represents noncontractile tissue that reduces stroke volume and strains the remaining myocardium. The stasis of blood in the aneurysm predisposes to mural thrombosis.

COMPLICATIONS IN CUTANEOUS WOUND HEALING

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excessive formation of the repair components  hypertrophic scar;  called a keloid

keloid

keloid keloid

COMPLICATIONS IN CUTANEOUS WOUND HEALING •

excessive formation of the repair components  exuberant granulation (proud flesh)  pyogenic granuloma  Raised red, soft, gingival lesions made up of excessive granulation tissue called.

COMPLICATIONS IN CUTANEOUS WOUND HEALING 1. • •

Deficient scar formation leads to poor scar formation and gaping of wounds as in Wound dehiscence and Nonhealing ulcers

Infected Post Operative Wound

Wound dehiscence

Case. This gentleman sustained burns from which he recovered, but is bothered by tight scars. He has limitation of motion from burn scar and webbing on his hand and his wrist......

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formation of contractures.

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Excessive contraction in the size of a wound cause contractures are commonly seen after serious burns and can cause restriction in the movement of joints

Overview of Repair Responses After Injury and Inflammation