5. Healing and Repair 2022.pdf

Healing and Repair Medicine1 (MED 201) – Pathology lecture Dr. Hassan Alahmadi Assistant Professor [email protected] Dr Ayesha Ahmed Associate Professor [email protected] Pathology Department College of Medicine – Imam Abdulrahman Bin Faisal University Learning Objectives ▪ Learn about differen...

Healing and Repair Medicine1 (MED 201) – Pathology lecture Dr. Hassan Alahmadi Assistant Professor [email protected] Dr Ayesha Ahmed Associate Professor [email protected] Pathology Department College of Medicine – Imam Abdulrahman Bin Faisal University Learning Objectives ▪ Learn about different tissue types; labile, stable, permanent ▪ Begin to understand how tissues repair occurs with an emphasis on labile and stable tissues ▪ Begin to understand the outcomes of tissue repair in labile, stable and permanent tissues Thursday, November 30, 2023 Thursday, November 30, 2023 Healing- Introduction ▪ Healing refers to the restoration of tissue architecture and function after an injury. ▪ Two types: – Regeneration: Replace the damaged components and return to a normal state – Repair: Replace the damaged tissue by connective fibrous tissue (scar formation) 4:20 Thursday, November 30, 2023 Thursday, November 30, 2023 Proliferative Capacities of Tissues Continuously Dividing Tissues (labile tissues) to Cells of these tissues are continuously being lost and replaced by maturation from stem cells and by gproliferation of mature cells. (ex hematopoietic cells in the bone marrow, surface epithelia) cells of these tissues are continuously being lost a 4:20 Thursday, November 30, 2023 Proliferative Capacities of Tissues 2. Stable Tissues Non deviding but when needed Cells of these tissues are quiescent Capable of proliferating in response to injury or loss of tissue mass Ex. parenchyma of most solid tissues (liver, kidney, and pancreas), endothelial cells, fibroblasts and smooth muscle cells 3. Permanent Tissues Non dividing The cells of these tissues are considered to be terminally differentiated and nonproliferative in postnatal life. Ex. Neurons and striated muscle cells (skeletal & heart muscle) In permanent tissues, repair is typically dominated by scar formation 4:20 Thursday, November 30, 2023 Regeneration in laibile in stable only ▪ In labile tissues, such as gut epithelium, and the skin, damage to epithelia can be corrected by the proliferation and differentiation of stem cells. ‫إعادة التجدد‬ .‫ يمكن تصحيح الضرر في الظهارة عن طريق تكاثر وتمايز الخاليا الجذعية‬،‫ مثل ظهارة األمعاء والجلد‬،‫▪ في األنسجة القابلة للتجدد‬ ▪ In stable tissue (parenchymal organs) especially the liver. ~ 50% of the liver may be removed in a transplantation which triggers a proliferative response of the remaining hepatocytes (compensatory growth). ‫ يمكن‬.‫ خاصة في الكبد‬،(‫في األنسجة الثابتة )األعضاء البارنكيمية‬ ‫ مما يثير‬،‫ من الكبد في عملية زراعة األعضاء‬٪50 ‫إزالة حوالي‬ .(‫استجابة تكاثرية للخاليا الكبدية املتبقية )النمو التعوضي‬ 4:20 Thursday, November 30, 2023 Healing with connective tissue (Repair) ▪ Severe or chronic tissue injury results in 1 damage to parenchymal cells - epithelia as well as the stromal framework (& ECM: extracellular matrix). ▪ Non-dividing cells injury. ▪ Starts with the formation of granulation tissue and culminates in the laying down of fibrous tissue. 4:20 Thursday, November 30, 2023 Granulation tissue ▪ The term granulation tissue derives from the pink, soft, granular gross appearance. ▪ Specialized type of tissue composed of: – – – – 4:20 Bloodvessels development New capillaries (angiogenesis) Loose ECM Inflammatory cells Fibroblasts fa.ITfI hetTfibroblast Thursday, November 30, 2023 TISSUE SEPARATION EPIDERMIS D E R M I S VESSELS LEAK BLOOD CLOTS VESSEL EPIDERMIS D E R M I S VESSELS LEAK BLOOD CLOTS VESSEL WBCs EMIGRATE SOURCES OF RECONSTRUCTIVE CELLS EPIDERMIS B L O O D C L O T WOUND KERATINOCYTES proliferate Proliferate and migrate ENDOTHELIAL CELLS proliferate angiogenesis FIBROBLASTS proliferate synthesize collagen & other ECM molecules Clot reduced to SCAB THIN EPITHELIUM new Basal lamina FIBROBLAST Collagen fibrils & fibers GRANULATION TISSUE formed CAPILLARY MACROPHAGE Repair by connective tissue 3 sequential processes: ▪ Angiogenesis: Formation of new blood vessels. ▪ Scar formation: – Migration and proliferation of fibroblasts – Deposition of ECM (collagen) & fibrosis. ▪ Remodeling: the scar. 4:20 Maturation and reorganization of Thursday, November 30, 2023 CUTANEOUS WOUND HEALING  Both epithelial regeneration and formation of connective tissue scar  Three main phases:  Inflammation  Formation of granulation tissue  ECM deposition and remodeling  These events overlap and cannot be completely separated from each other.  Based on the nature of the wound, the healing can occur by first or second intention 4:20 Thursday, November 30, 2023 Thursday, November 30, 2023 Healing by first intention ▪ Ex. Clean, uninfected surgical incision approximated by surgical sutures ▪ The incision causes only focal disruption of epithelial basement membrane continuity and death of a relatively few epithelial and connective tissue cells. ▪ A small scar is formed. ▪ Minimal wound contraction. 4:20 Thursday, November 30, 2023 I Thursday, November 30, 2023 Healing by first intention • The narrow incisional space first fills with fibrin-clotted blood. • Within 24 hours, neutrophils are seen •Basal cells at the cut edge of the epidermis begin to show increased mitotic activity. •Epithelial cells from both edges begin to migrate and proliferate to meet in the midline. •By day 3, granulation tissue appear •Collagen fibers are now evident at the incision margins, but vertically oriented and do not bridge the incision. •Epithelial cell proliferation continues. •By day 5, Collagen fibers become more abundant and begin to bridge the incision. •During the second week, "blanching" begins by increasing collagen deposition and the regression of vascular channels. 4:20 Thursday, November 30, 2023 Healing by Second Intention When cell or tissue loss is more extensive: Large wounds, abscess formation, and ulceration. Differs from primary healing by: 1. larger clot 2. Inflammatory reaction is more intense 3. Abundant development of granulation tissue 4. Wound contraction by the action of myofibroblasts : For example, Within 6 weeks, large skin defects may be reduced to 10% of z their original size. 5. Formation of a large scar 4:20 Thursday, November 30, 2023 4:20 Final stage PATHOLOGIC ASPECTS OF REPAIR Factors delaying wound healing Wound healing may be altered by a variety of influences: 1. Infections : Cause delay in healing – prolongs the inflammation phase & – increases the local tissue injury. 2. 4:20 Nutrition: Protein deficiency, for example, and particularly vitamin C deficiency, inhibits collagen synthesis and retards healing. Thursday, November 30, 2023 3. Glucocorticoids (steroids): Result in poor wound strength due to diminished fibrosis 4. Poor perfusion, due to arteriosclerosis or diabetes: impairs healing. 5. Foreign bodies such as fragments of steel, glass, or bone impede healing. 4:20 Thursday, November 30, 2023 I 2 2 I 3 4 PATHOLOGIC ASPECTS OF REPAIR complications Aberrations of cell growth and ECM production: 1. Accumulation of exuberant amounts of collagen can give rise to prominent, raised scars known as keloids 2. Exuberant (excessive) granulation tissue that protrudes above the level of the surrounding skin and prevent reepithelialization. Requires resection. 4:20 Thursday, November 30, 2023 Deficient scar formation: Wound dehiscence Exaggeration of wound contraction contracture Thursday, November 30, 2023 Healing in specific tissues (heart) ▪ Cardiac myocytes are permanent cells. They do not divide, and the heart thus heals by collagenous scar formation. so Thursday, November 30, 2023 Healing in specific tissues (kidney) ▪ The kidney has limited regenerative capacity. ▪ It is maximal in the cortical tubules, less in medullary tubules, and non-existent in glomeruli. ▪ If the extracellular matrix (tubule basement membrane) is not destroyed, then the tubular epithelium is capable of complete regeneration. Thursday, November 30, 2023 Healing in specific tissues (liver) ▪ The liver normally heals by regeneration. ▪ It can regenerate perhaps 75% of its volume ▪ Scarring occurs when the extracellular matrix of the liver is damaged by repeated or severe injury. ▪ Bile ducts then proliferate, regenerative nodules form, and collagenous scars become evident. ▪ This scarring process is commonly called cirrhosis. Thursday, November 30, 2023 Thursday, November 30, 2023 Thursday, November 30, 2023 Healing in specific tissues (brain) ▪ The brain heals by a process known as gliosis. ▪ Astrocytes proliferate and form what is called a glial scar. ▪ The only exception to this is in the process of abscess formation, where fibroblasts from cerebral blood vessels form a collagenous scar. ▪ This scar may later serve as a focus for epileptic seizures. Thursday, November 30, 2023 Thank you Thursday, November 30, 2023