WOUUNDx FOR THIS ACCIEDENTAL INJURY OCCURED

THIS IS FOR EDDUCATIOONNAL PURPOSE ESPECIALLY THE PEOPLE EHO ARE INTERESTED FOR AND ALSO INCLUDES FOR VLOGGERS WHO ARE TAKING CARE FOR THE ABOVE HOSPPPIYRA A

1. USMLE PATHOLOGY

2. Faculty Introduction Dr. Gangadhara Swamy Gajula MBBS., MD Professor of Pathology Dr Gangadhara did his MBBS and MD from Government Medical colleges in India . After working in various positions in Indian medical colleges , shifted to Malaysia and presently working as Professor of Pathology in a Deemed to be University in Malaysia. He did a certificate course in medical education from UK. Many articles are published in various National and International Indexed Journals. He also achieved Best Teacher Award.

3. Path-5 Wound healing & Repair

4. Learning outcomes At the end of this session the student would be able to Classify the cells according to their regenerating capacity Describe wound healing and its types Outline mechanisms of wound healing Discuss factors affecting wound healing List complications of wound healing

5. Outcomes of acute inflammation

6. Types of cell based on their regenerative capacity 6 LABILE CELLS ( continuously dividing tissues cells / proliferate throughout life) replace continuously the destroyed cells surface epithelia such as stratified squamous epithelia of the skin, oral cavity & vagina columnar epi; of GIT , Uterus, Fallopian tubes splenic, lymphoid & haemopoietic cells

7. 2. STABLE CELLS 7 low level of replication capable of reconstituting tissue of origin basement membrane is necessary for organized regeneration Parenchymal cells of liver, kidneys, and pancreas Mesenchymal cells such as fibroblasts and smooth muscle; vascular endothelial cells Permanent cells (NON- dividing cells) not undergo mitotic division in post- natal life nerve cells skeletal and cardiac muscle cells

8. Regeneration refers to the proliferation of cells and tissues to replace the lost structures. Repair consists of a combination of regeneration and scar formation by the deposition of collagen. 8

9. GRANULATION TISSUE As early as 24 hours after injury, fibroblasts & vascular endothelial cells proliferate to form (by 3-5 days) - the specialized type of tissue - GRANULATION TISSUE ( Hallmark of healing ) 9 Gross  pink, soft granular appearance on surface of wound Histology  composed of proliferation of fibroblasts & small blood vessels & mononuclear cells

10. New vessels originate by budding or sprouting of pre- existing vessel - a process called ANGIOGENESIS OR NEOVASCULARIZATION These new vessels have leaky inter- endothelial junctions. Therefore newly formed granulation tissue is oedematous . Inflammatory cells are also seen. 10

11. 11

12. Repair by connective tissue deposition includes the following basic features: Haemostasis Inflammation (to remove dead and damaged tissue) Angiogenesis & formation of granulation tissue Wound contraction Tissue remodelling Increase in wound strength (scar = fibrosis) 12

13. WOUND HEALING 13 A process by which lost or destroyed cells are replaced by viable cells after injury. PRIMARY UNION (healing by first intention ) SECONDARY UNION (healing by second intention) 1. PRIMARY UNION can be seen in healing of clean surgical incision Healing occurs without bacterial contamination & minimal loss of tissue Incision space is narrow & immediately filled with clotted blood Dehydration of surface clot  scab

14. Within 24 Hours Neutrophils appear at the margin of incision Proliferation of epidermis at the cut edges Within 24 – 48 Hours Spurs of epithelial cells from edges, grow along cut margins of dermis to fuse in midline as continuous thin epithelial layer. By Day 3 Neutrophils are replaced by macrophage Granulation tissue appears Collagen fibers - present in margins of incision , vertically oriented & do not bridge incision. Epithelial cells - continue proliferation 14

15. By day 5 Collagen bridges the incision Epidermis becomes thickened and recovers normal thickness By 2 nd week Continued proliferation of collagen & fibroblasts Leukocytes & edema disappears By the end of 1st month Scar (cellular connective tissue, intact epidermis) Dermal appendages that have been destroyed in line of incision permanently lost. A Year : Scar  acellular, avascular, pale collagenous scar 15

16. 2. SECONDARY UNION (healing by 2nd intention) 16 Can be seen in healing of     infarction inflammatory ulceration abscess surface wound with large defects The common denominator is large tissue defect that must be filled. Regeneration of parenchymal cells cannot completely reconstitute the original architecture . Abundant granulation tissues

17. SECONDARY HEALING DIFFERS FROM PRIMARY HEALING IN: 17 Loss of greater amount of tissue Greater loss of skin appendages More intense inflammation Production of greater amount of inflammatory exudate & necrotic debris Formation of larger amount of granulation tissue Contraction of surface wound Production of large amount of scar Slower completion of entire healing process Contracted wound results in rapid healing since lesser surface area of the injured tissue has to be replaced

18. Primary healing 18 Vs Secondary healing

19. Complications of Wound Healing 19 Infection Wound Dehiscence & ulceration Due to inadequate formation of granulation tissue Hypertrophic scar Accumulation of excessive collagen  raised scar Keloid formation if the scar grows beyond the boundaries of the original wound and does not regress , it is called a keloid (excess type III collagen) Proud Flesh; caused by excessive granulation tissue Contracture: due to reduction of scar size in severe skin burns

20. Wound dehiscence Keloid Contracture 20

21. Factors Influencing Inflammatory Repair Rate 21 I. Systemic Factors: Age Healing in old age is slower than young 2. Immunity Immunosuppression  impairs the wound healing (WH) Nutrition: Protein deficiency - reduces formation of granulation tissue & collagen Vitamin C deficiency – reduces collagen synthesis Zinc deficiency – enzymes are zinc dependent  delayed WH

22. 4. Hematological derangements: Neutropenia, Hemophilia  delays repair 22 Diabetes mellitus:  blood glucose  prone to infection  delays repair Hormones: Corticosteroids  impair inflammatory response  delay WH Temperature: Healing slows in cold weather Rate of wound healing is directly proportional to T° of environment

23. II. Local Factors: Infection  delayed wound healing Types of injured tissue If injury occurs in labile cells & stable cells , repair process is rapid. In permanent cells  Scarring Type, size, location of wound Type - A clean aseptic wound heals faster than an infected wound Size - Small wound heals faster than larger ones Location - Highly vascularized area heals faster Adhesion to bony surface – When the wound adhere to bony surface prevent wound contraction  delay repair. 23

24. Foreign bodies  delay repair. Movements  delay healing. Exposure to UV light  promotes healing Exposure to ionizing radiation  delays healing Proper coaptation of wound margin  speeds healing of incision Direction of wound Skin wound made a direction parallel to lines of Langer heals faster (due to orientation of collagen bundles in dermis) 24

25. Take home message…. Labile tissues possess stem cells that continuously cycle to regenerate the tissue. 1. Small and large bowel (stem cells in mucosal crypts) 2. Skin (stem cells in basal layer) 3. Bone marrow (hematopoietic stem cells) Stable tissues are comprised of cells that are quiescent {G_), but can reenter the cell cycle to regenerate tissue when necessary. Permanent tissues lack significant regenerative potential (e.g., myocardium, skeletal muscle, and neurons).

26. scar formation, in which type III collagen is replaced with type 1 collagen 1. Type III collagen is pliable and present in granulation tissue, embryonic tissue, uterus, and keloids. 2. Type I collagen has high tensile strength and is present in skin, bone, tendons, and most organs, 3. Collagenase removes type III collagen and requires zinc as a cofactor.

27. Vitamin C is an important cofactor in the hydroxylation of proline and lysine procollagen residues; hydroxylation is necessary for eventual collagen cross-linking . ii. Copper is a cofactor for lysyl oxidase, which cross-links lysine and hydroxy lysine to form stable collagen. iii. Zinc is a cofactor for collagenase, which replaces the type III collagen of granulation tissue with stronger type I collagen.

28. Tissue mediators MEDIATOR ROLE FGF Stimulates angiogenesis TGF- β Angiogenesis, fibrosis VEGF Stimulates angiogenesis PDGF Secreted by activated platelets and macrophages Induces vascular remodeling and smooth muscle cell migration ,Stimulates fibroblast growth for collagen synthesis Metalloproteinases Tissue remodeling EGF Stimulates cell growth via tyrosine kinases ( eg , EGFR/ErbB1)

29. How frequently does the epidermis typically regenerate? a. 1–3 weeks b 4–6 weeks c. 7–9 weeks d. 10–12 weeks

30. Up to 75% of the skin's total dry weight is composed of a.  elastin. b.  collagen. c.  keratin. d.  sebum.

31. The outermost layer of the epidermis is termed the stratum a. corneum. b. granulosum. c. spinosum. d. basale .

32. Which of the following is the correct sequential order of the phases of healing? a.  Remodeling, inflammation, hemostasis, and repair b.  Inflammation, hemostasis, proliferation, and maturation c.  Hemostasis, inflammation, repair, and remodeling d.  Inflammation, maturation, proliferation, and hemostasis

33. With regard to wound healing a. macrophage infiltration occurs at 24 hours b. wound strength is 25% of normal by end of the 1st week c. type I collagen is replaced by type III collagen d. neovascularisation is maximal at day 5 e. all of the above

34. A 48-year-old male who has a long history of excessive drinking presents with signs of alcoholic hepatitis. Microscopic examination of a biopsy of this patient’s liver reveals irregular eosinophilic hyaline inclusions within the cytoplasm of the hepatocytes. These eosinophilic inclusions are composed of Immunoglobulin Excess plasma proteins Prekeratin intermediate filaments Basement membrane material

35. A 7-year-old female presents to the pediatrician with a 12-hr history of headache, cough, runny nose, and headache. Her current temperature is 100.2°F. Physical exam is positive for clear nasal discharge, frontal sinus tenderness with palpation, and cervical lymphadenopathy. Her past medical history is positive for a urinary tract infection two weeks ago that was resolved with antibiotics. Laboratory studies show a leukocyte count of 2700/mm3 with 30% segmented neutrophils. The medication responsible for her isolated moderate neutropenia works via which of the following mechanisms? A. Inhibition of bacterial folic acid synthesis B. Decreasing peptidoglycan crosslinking C. Blocks incoming aminoacyl-tRNA D. Bind to 23S rRNA E. Causes single-stranded breaks in DNA F. Competitive antagonism of para-aminobenzoic acid

36. REFERENCES Vinay Kumar, Abul Abbas, Jon Aster, Andrea T. and Abhijit Das. Robbins & Kumar Basic Pathology, 11th Edition. Elsevier, 2023 ISBN: 978-0-323-79019- 2 Vinay Kumar, Abul K. Abbas and Jon C. Aster. Robbins & Cotran Pathologic Basis of Disease, 10th Edition. Elsevier, 2021 ISBN: 978-0-323-53113- 9 https://www.proprofs.com/quiz-school/story.php?title=chapter-15-wound-healing https://ksumsc.com/download_center/Archive/3rd/438/Surgery%20/Teamwork%20/1st%20semester/4%20Wound%20Healing%20_%20Management%20%28updated%29.pdf https://www.osmosis.org/notes/Skin_Structures#page-1 Dentosphere : World of Dentistry: MCQs on General Pathology - Wound Healing and Repair (dentaldevotee.com) 31-Jul- 23 23