Tissue Repair and Tissue Healing Pathology

Tissue healing pathology

1. Tissue repair & HEALING PRESENTATION BY – MOKSH SOLANKI AAKASH PATIL CHANDRAKANT LAHANE KUNAL TITKARE RAJ MAHAJAN SHASHANK JADHAV

2. healing HEALING IS THE BODY’S RESPONSE TO INJURY IN AN ATTEMPT TO RESTORE NORMAL STRUCTURE AND FUNCTION. IT INVOLVES 2 PROCESSES: REGENERATION WHEN HEALING TAKES PLACE BY PROLIFERATION OF PARENCHYMAL CELLS AND USUALLY RESULTS IN COMPLETE RESTORATION OF THE ORIGINAL TISSUES. REPAIR WHEN HEALING TAKES PLACE BY PROLIFERATION OF CONNECTIVE TISSUE RESULTING IN FIBROSIS AND SCARRING. AT TIMES, BOTH THESE PROCESSES TAKE PLACE SIMULTANEOUSLY.

3. REGENERATION SOME PARENCHYMAL CELLS ARE SHORT-LIVED WHILE OTHERS HAVE A LONGER LIFESPAN. IN ORDER TO MAINTAIN PROPER STRUCTURE OF TISSUES, THESE CELLS ARE UNDER THE CONSTANT REGULATORY CONTROL OF THEIR CELL CYCLE. DEPENDING UPON THEIR CAPACITY TO DIVIDE, THE CELLS OF THE BODY CAN BE DIVIDED INTO 3 GROUPS: LABILE CELLS STABLE CELLS PERMANENT CELLS

4. 1. LABILE CELLS - THESE CELLS CONTINUE TO MULTIPLY THROUGHOUT LIFE UNDER NORMAL PHYSIOLOGIC CONDITIONS. THESE INCLUDE: SURFACE EPITHELIAL CELLS OF THE EPIDERMIS, ALIMENTARY TRACT, RESPIRATORY TRACT, URINARY TRACT, VAGINA, CERVIX, UTERINE ENDOMETRIUM, HAEMATOPOIETIC CELLS OF BONE MARROW AND CELLS OF LYMPH NODES AND SPLEEN. 2. STABLE CELLS - THESE CELLS DECREASE OR LOSE THEIR ABILITY TO PROLIFERATE AFTER ADOLESCENCE BUT RETAIN THE CAPACITY TO MULTIPLY IN RESPONSE TO STIMULI THROUGHOUT ADULT LIFE. THESE INCLUDE: PARENCHYMAL CELLS OF ORGANS LIKE LIVER, PANCREAS, KIDNEYS, ADRENAL AND THYROID; MESENCHYMAL CELLS LIKE SMOOTH MUSCLE CELLS, FIBROBLASTS, VASCULAR ENDOTHELIUM, BONE AND CARTILAGE CELLS. 3. PERMANENT CELLS - THESE CELLS LOSE THEIR ABILITY TO PROLIFERATE AROUND THE TIME OF BIRTH. THESE INCLUDE: NEURONS OF NERVOUS SYSTEM, SKELETAL MUSCLE AND CARDIAC MUSCLE CELLS.

5. RELATIONSHIP OF PARENCHYMAL CELLS WITH CELL CYCLE PARENCHYMAL CELLS IN RELATION TO CELL CYCLE (G0–RESTING PHASE; G1, G2–GAPS; S–SYNTHESIS PHASE; M–MITOSIS PHASE). THE INNER CIRCLE SHOWN WITH GREEN LINE REPRESENTS CELL CYCLE FOR LABILE CELLS; CIRCLE SHOWN WITH YELLOW-ORANGE LINE REPRESENTS CELL CYCLE FOR STABLE CELLS; AND THE CIRCLE SHOWN WITH RED LINE REPRESENTS CELL CYCLE FOR PERMANENT CELLS. COMPARE THEM WITH TRAFFIC SIGNALS —GREEN STANDS FOR ‘GO’ APPLIES HERE TO DIVIDING LABILE CELLS; YELLOWORANGE SIGNAL FOR ‘READY TO GO’ APPLIES HERE TO STABLE CELLS WHICH CAN BE STIMULATED TO ENTER CELL CYCLE; AND RED SIGNAL FOR ‘STOP’ HERE MEANS NON-DIVIDING PERMANENT CELLS.

6. REPAIR REPAIR IS THE REPLACEMNET OF INJURED TISSUE BY FIBROUS TISSUE. TWO PROCESSES ARE INVOLVED IN REPAIR : GRANNULATION TISSUE FORMATION WOUND CONTRACTION AND STRENGTH REPAIR RESPONSE TAKES PLACE BY PARTICIPATION OF MESENCHYMAL CELLS (CONSISTING OF CONNECTIVE TISSUE STEM CELLS, FIBROCYTES, AND HISTOCYTES), ENDOTHELIAL CELLS, MACROPHAGES, PLATELETS, AND THE PARENCHYMAL CELLS OF THE INJURED ORGAN.

7. GRANULATION TISSUE FORMATION THE TERM GRANULATION TISSUE DERIVES ITS NAME FROM SLIGHTLY GRANULAR AND PINK APPEARANCE OF THE TISSUE. EACH GRANULE CORRESPONDS HISTOLOGICALLY TO PROLIFERATION OF NEW SMALL BLOOD VESSELS WHICH ARE SLIGHTLY LIFTED ON THE SURFACE AND HAS THIN COVERING OF FIBROBLAST AND YOUNG COLLAGEN.

8. PROCESS OF GRANULATION TISSUE FORMATION PROCESS OF GRANULATON TISSUE FORMATION CAN BE DIVIDED INTO FOLLOWING FOUR PHASES – BLEEDING PHASE INFLAMMATORY PHASE PROLIFERATION PHASE REMODELLING PHASE

9. ACTIVE GRANULATION TISSUE HAS INFLAMMATORY CELL INFILTRATE, NEWLY FORMED BLOOD VESSELS AND YOUNG FIBROUS TISSUE IN LOOSE MATRIX GRANULATION TISSUE FORMATION

10. BLEEDING PHASE FOLLOWING TRAUMA, THERE IS BLEEDING WHICH MAY STOP AFTER A FEW HOURS (ON AN AVERAGE WITHIN 4-6 HOURS) BUT MAY VARY, FOLLOWED BY CLOTTING OF BLOOD AT THE SITE OF INJURY.

11. INFLAMMATORY PHASE INFLAMMATION IS AN ESSENTIAL COMPONENT OF HEALING PROCESS. AFTER BLOOD CLOTTING, FIBRIN AND FIBRONECTIN REMAIN IN THE TISSUES WHICH FORM THE SUBSTRATE FOR ADHESION OF VARIOUS INFLAMMATORY CELLS. INFLAMMATORY RESPONSE INVOLVES VASCULAR AND CELLULAR PHASE, AND IS REGULATED BY CHEMICAL MEDIATORS. INITIALLY, THERE IS INFILTRATION BY PMS AND FLUID EXUDATES WITHIN A FEW HOURS, FOLLOWED BY INFLUX OF PHAGOCYTIC CELLS (MACROPHAGES, MONOCYTES) WITHIN 24 HOURS.

12. Proliferative phase THIS PHASE INVOLVES GENERATION OF REPAIR MATERIAL THAT FORMS THE INITIAL GRANULATION TISSUE. IT BEGINS WITHIN FIRST 1-2 DAYS AFTER INJURY AND REACHES ITS PEAK AT 2-3 WEEKS BUT QUALITATIVELY STRONG SCAR IS FORMED MUCH LATER AFTER TRAUMA (4-6 MONTHS). THIS PHASE CONSISTS OF 2 MAIN PROCESSES: ANGIOGENESIS OR NEOVASCULARISATION, AND FIBROGENESIS.

13. angiogenesis FORMATION OF NEW BLOOD VESSELS AT THE SITE OF INJURY TAKES PLACE BY PROLIFERATION OF ENDOTHELIAL CELLS FROM THE MARGINS OF SEVERED BLOOD VESSELS. BLOOD VESSELS DIFFERENTIATE INTO MUSCULAR ARTERIOLES, THIN WALLED VENULES AND TRUE CAPILLARIES. THE PROCESS OF ANGIOGENESIS IS STIMULATED WITH PROTEOLYTIC DESTRUCTION OF BASEMENT MEMBRANE. ANGIOGENESIS TAKES PLACE UNDER THE INFLUENCE OF FOLLOWING FACTORS: 1. VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) ELABORATED BY MESENCHYMAL CELLS WHILE ITS RECEPTOR, (VEGF-R) IS PRESENT IN ENDOTHELIAL CELLS ONLY. 2. PLATELET-DERIVED GROWTH FACTOR (PDGF), TRANSFORMING GROWTH FACTOR- (TGF-ß), BASIC FIBROBLAST GROWTH FACTOR (B-FGF) AND SURFACE INTEGRINS ARE ALL ASSOCIATED WITH CELLULAR PROLIFERATION.

14. Fibrogenesis   THE NEWLY FORMED BLOOD VESSELS ARE PRESENT IN AN AMORPHOUS GROUND SUBSTANCE OR MATRIX. THE NEW FIBROBLAST FEATURES INTERMEDIATE BETWEEN THOSE OF FIBROBLAST AND SMOOTH MUSCLES CELLS (MYOFIBROBLASTS).

15. REMODELLING PHASE THIS PHASE BEGINS AROUND THE TIME WHEN PROLIFERATION PHASE IS AT PEAK (I.E. 2-3 WEEKS FOLLOWING INJURY). THE MAIN EVENTS IN REMODELLING ARE REFINEMENT OF COLLAGEN AND ITS ASSOCIATED EXTRACELLULAR MATRIX. THE REPLACED TYPE I COLLAGEN FIBRILS HAVE MORE CROSS-LINKS AND GREATER TENSILE STRENGTH. THIS RESULTS IN FORMATION OF INACTIVE LOOKING SCAR; THIS PROCESS IS KNOWN AS CICATRISATION.

16. FACTORS INFLUENCING TISSUE REPAIR WHILE SEVERAL FACTORS DELAY AND STIMULATE HEALING THEY ARE : LOCAL FACTORS GENERAL FACTORS THERAPEUTIC INFLUENCES

17. LOCAL FACTORS FOLLOWING FACTORS ACTING LOCALLY DELAY WOUND HEALING: 1. INFECTION IS THE MOST IMPORTANT FACTOR ACTING LOCALLY THAT DELAYS THE PROCESS OF HEALING. 2. POOR BLOOD SUPPLY TO WOUND AND ISCHAEMIA SLOW HEALING E.G INJURIES TO FACE HEAL QUICKLY DUE TO RICH BLOOD SUPPLY WHILE INJURY TO LEG WITH VARICOSE ULCERS HAVING POOR BLOOD SUPPLY HEALS SLOWLY. 3. FOREIGN BODIES INCLUDING SUTURES INTERFERE WITH HEALING AND CAUSE INTENSE INFLAMMATORY REACTION AND INFECTION. 4. MOVEMENT DELAYS WOUND HEALING. 5. EXPOSURE TO IONISING RADIATION DELAYS GRANULATION TISSUE FORMATION. 6. EXPOSURE TO ULTRAVIOLET LIGHT FACILITATES HEALING.

18. GENERAL FACTORS A FEW GENERAL FACTORS INFLUENCE HEALING: 1. AGE WOUND HEALING IS RAPID IN YOUNG AND SOMEWHAT SLOW IN AGED AND DEBILITATED PEOPLE DUE TO POOR BLOOD SUPPLY TO THE INJURED AREA IN THE LATTER. 2. NUTRITION DEFICIENCY OF CONSTITUENTS LIKE PROTEIN, VITAMIN C (SCURVY), VITAMIN A AND ZINC DELAYS THE WOUND HEALING. 3. SYSTEMIC INFECTION DELAYS WOUND HEALING. 4. ADMINISTRATION OF GLUCOCORTICOIDS AND NSAIDS DELAY WOUND HEALING. 5. UNCONTROLLED DIABETICS ARE MORE PRONE TO DEVELOP INFECTIONS AND HENCE DELAYED HEALING OF WOUNDS. 6. HAEMATOLOGIC ABNORMALITIES LIKE DEFECT OF NEUTROPHIL FUNCTIONS (CHEMOTAXIS AND PHAGOCYTOSIS), AND NEUTROPENIA AND BLEEDING DISORDERS SLOW THE PROCESS OF WOUND HEALING. 7. COLDER TEMPERATURE DELAYS HEALING.

19. THERAPEUTIC INFLUENCES 1. IF THERE IS DELAYED HEALING, APPROPRIATE THERAPY MAY BE EMPLOYED WHICH STIMULATES HEALING BY MORE EFFICIENT RESPONSE BUT DOES NOT CHANGE THE NATURAL PROCESS OF HEALING. 2. THERAPY WORKS BY INFLUENCING THE CHEMICAL ENVIRONMENT OF THE REPAIR TISSUE TO BRING HEALING BACK ON TRACK IF THERE IS DELAYED HEALING BUT THERAPY IS NOT INDICATED IF THE HEALING IS PROCEEDING NORMALLY. 3. THESE INCLUDE USE OF EXERCISE THERAPY, MANUAL THERAPY, ELECTROTHERAPY ETC.

20. FRACTURE HEALING HEALING OF FRACTURE BY CALLUS FORMATION DEPENDS UPON SOME CLINICAL CONSIDERATIONS WHETHER THE FRACTURE IS: TRAUMATIC OR PATHOLOGICAL COMPLETE OR INCOMPLETE SIMPLE, COMMUNICATED OR COMPOUND BASIC EVENTS IN HEALING OF ANY TYPE OF FRACTURE ARE : PRIMARY UNION SECONDARY UNION

21. PRIMARY UNION PRIMARY UNION OF FRACTURES OCCURS WHEN THE ENDS OF FRACTURE ARE APPROXIMATED SURGICALLY BY APPLICATION OF COMPRESSION CLAMPS OR METAL PLATES. IN THESE CASES, BONY UNION TAKES PLACE WITH FORMATION OF MEDULLARY CALLUS WITHOUT PERIOSTEAL CALLUS FORMATION. THE PATIENT CAN BE MADE AMBULATORY EARLY BUT THERE IS MORE EXTENSIVE BONE NECROSIS AND SLOW HEALING.

22. SECONDARY UNION SECONDARY UNION IS MORE COMMON FORM OF FRACTURE HEALING WHEN THE PLASTER CASTS ARE APPLIED FOR IMMOBILISATION OF A FRACTURE. THOUGH IT IS A CONTINUOUS PROCESS, SECONDARY BONE UNION IS DESCRIBED UNDER THE FOLLOWING 3 HEADINGS: I) PROCALLUS FORMATION II) OSSEOUS CALLUS FORMATION III) REMODELLING

23. FRACTURE HEALING FRACTURE HEALING. A, HAEMATOMA FORMATION AND LOCAL INFLAMMATORY RESPONSE AT THE FRACTURE SITE. B, INGROWTH OF GRANULATION TISSUE WITH FORMATION OF SOFT TISSUE CALLUS. C, FORMATION OF PROCALLUS COMPOSED OF WOVEN BONE AND CARTILAGE WITH ITS CHARACTERISTIC FUSIFORM APPEARANCE AND HAVING 3 ARBITRARY COMPONENTS—EXTERNAL, INTERMEDIATE AND INTERNAL CALLUS. D, FORMATION OF OSSEOUS CALLUS COMPOSED OF LAMELLAR BONE FOLLOWING CLEARANCE OF WOVEN BONE AND CARTILAGE. E, REMODELLED BONE ENDS; THE EXTERNAL CALLUS CLEARED AWAY. INTERMEDIATE CALLUS CONVERTED INTO LAMELLAR BONE AND INTERNAL CALLUS DEVELOPING BONE MARROW CAVITY.

24. PROCALLUS FORMATION STEPS INVOLVED IN THE FORMATION OF PROCALLUS ARE AS FOLLOWS: 1. HAEMATOMA FORMS DUE TO BLEEDING FROM TORN BLOOD VESSELS, FILLING THE AREA SURROUNDING THE FRACTURE. LOOSE MESHWORK IS FORMED BY BLOOD AND FIBRIN CLOT WHICH ACTS AS FRAMEWORK FOR SUBSEQUENT GRANULATION TISSUE FORMATION. 2. LOCAL INFLAMMATORY RESPONSE OCCURS AT THE SITE OF INJURY WITH EXUDATION OF FIBRIN, POLYMORPHS AND MACROPHAGES. THE MACROPHAGES CLEAR AWAY THE FIBRIN, RED BLOOD CELLS, INFLAMMATORY EXUDATE AND DEBRIS. FRAGMENTS OF NECROSED BONE ARE SCAVENGED BY MACROPHAGES AND OSTEOCLASTS. 3. INGROWTH OF GRANULATION TISSUE BEGINS WITH NEOVASCULARISATION AND PROLIFERATION OF MESENCHYMAL CELLS FROM PERIOSTEUM AND ENDOSTEUM. A SOFT TISSUE CALLUS IS THUS FORMED WHICH JOINS THE ENDS OF FRACTURED BONE WITHOUT MUCH STRENGTH

25. 4. CALLUS COMPOSED OF WOVEN BONE AND CARTILAGE STARTS WITHIN THE FIRST FEW DAYS . THE CELLS OF INNER LAYER OF THE PERIOSTEUM HAVE OSTEOGENIC POTENTIAL AND LAY DOWN COLLAGEN AS WELL AS OSTEOID MATRIX IN THE GRANULATION TISSUE. THIS STAGE IS CALLED PROVISIONAL CALLUS OR PROCALLUS FORMATION AND IS ARBITRARILY DIVIDED INTO EXTERNAL, INTERMEDIATE AND INTERNAL PROCALLUS. CALLUS FORMATION IN FRACTURE HEALING.

26. OSSEOUS CALLUS FORMATION THE PROCALLUS ACTS AS SCAFFOLDING ON WHICH OSSEOUS CALLUS COMPOSED OF LAMELLAR BONE IS FORMED. THE WOVEN BONE IS CLEARED AWAY BY INCOMING OSTEOCLASTS AND THE CALCIFIED CARTILAGE DISINTEGRATES. IN THEIR PLACE, NEWLY-FORMED BLOOD VESSELS AND OSTEOBLASTS INVADE, LAYING DOWN OSTEOID WHICH IS CALCIFIED AND LAMELLAR BONE IS FORMED BY DEVELOPING HAVERSIAN SYSTEM CONCENTRICALLY AROUND THE BLOOD VESSELS.

27. REMODELLING DURING THE FORMATION OF LAMELLAR BONE, OSTEOBLASTIC LAYING AND OSTEOCLASTIC REMOVAL ARE TAKING PLACE REMODELLING THE UNITED BONE ENDS, WHICH AFTER SOMETIME, IS INDISTINGUISHABLE FROM NORMAL BONE. THE EXTERNAL CALLUS IS CLEARED AWAY, COMPACT BONE (CORTEX) IS FORMED IN PLACE OF INTERMEDIATE CALLUS AND THE BONE MARROW CAVITY DEVELOPS IN INTERNAL CALLUS.

28. Complications of Fracture Healing THESE ARE AS UNDER: 1. FIBROUS UNION MAY RESULT INSTEAD OF OSSEOUS UNION IF THE IMMOBILISATION OF FRACTURED BONE IS NOT DONE. OCCASIONALLY, A FALSE JOINT MAY DEVELOP AT THE FRACTURE SITE (PSEUDO-ARTHROSIS). 2. NON-UNION MAY RESULT IF SOME SOFT TISSUE IS INTERPOSED BETWEEN THE FRACTURED ENDS. 3. DELAYED UNION MAY OCCUR FROM CAUSES OF DELAYED WOUND HEALING IN GENERAL SUCH AS INFECTION, INADEQUATE BLOOD SUPPLY, POOR NUTRITION, MOVEMENT AND OLD AGE.