Inflammation and Tissue Repair PDF

SERIOSA 01/22/2025 Body cannot remove the organism. It persists until it worsens. LEGEND TOPIC...

SERIOSA 01/22/2025 Body cannot remove the organism. It persists until it worsens. LEGEND TOPIC Sample case: HIV SUBTOPIC T-Helper cells / CD4 cells ​ PPT content signal the body of ongoing ➔​ Supplementary Notes infection / inflammation. HIV virus destroys these cells which means the body won’t be INFLAMMATION AND TISSUE REPAIR alerted to infection or inflammation. Therefore, in INFLAMMATION individuals with HIV, even a ​ response of a vascularized tissue simple cough or cold can that delivers leukocytes and become serious because these molecules of host defense from the protective mechanisms are circulation to the sites of infection compromised. and cell damage in order to eliminate the offending agent. ➔​ Body’s goal is to always ➔​ End goal of inflammation: maintain homeostasis eliminate offending agent (microorganism) ➔​ When eliminating something, you have to repair it, thus inflammation and tissue repair ​ Mediators - phagocytic leukocytes, antibodies, complement proteins. ➔​ Makes inflammation happen ➔​ Most important characteristic is its ability to phagocytize– clearing or eating up microorganisms on the site of inflammation. ​ The inflammatory response is actually more beneficial than what is commonly known about it. ➔​ Inflammation has a negative notion but it's actually a positive response to eliminate organisms. ➔​ What happens if the body doesn’t have an inflammatory INFLAMMATION: SEQUENTIAL response anymore? EVENTS 1.​ RECOGNITION - of noxious stimuli that is the initiating stimulus  ➔​ Body has to recognize the ➔​ e.g. Allergy brought about by offending agent histamine ; causes swelling 2.​ RECRUITMENT - leukocytes, and hives plasma proteins go into the tissue ➔​ Autoimmune disorder - If the ➔​ When the body recognizes cell doesn’t recognize itself. ongoing inflammation, it will send out mediators (neutrophils, macrophages) to the site and recruit more. 3.​ REMOVAL - of the offending agent 4.​ REGULATION - termination of the inflammatory pathway ➔​ Inflammation responses shouldn/t always be active– pathway needs to be regulated. 5.​ REPAIR - series of events that ➔​ Susceptible host (e.g. patient) heal damaged tissue ➔​ Means of entry (e.g. wound) ➔​ Means of exit (e.g. nose, CAUSES OF INFLAMMATION mouth, feces, anus) ​ INFECTION - Different microorganisms mount different RECOGNITION OF MICROBES AND inflammatory responses. Extent of DAMAGED CELL the damage could be due to the ​ Recognition of microbial offending agent, the host immune components or substances system, or both. released from damaged cells is the ➔​ No. 1 cause initiating step in inflammatory ➔​ Presence offending agent reactions. causing infection ​ Cellular receptors for microbes: ➔​ e.g. Tooth decay caused by cells express receptors in the Streptococcus mutans plasma membrane (extracellular ​ TISSUE NECROSIS - elicits microbes), endosomes (ingested inflammation regardless of the microbes), and cytosol cause of cell death (DAMPS) (intracellular microbes). ➔​ DAMPS - recognized by the ➔​ Receptors recognize the body on instances of necrosis foreign bodies ​ FOREIGN BODIES - elicits ➔​ Endosomes - microorganisms inflammation by themselves or were engulfed by phagocytes; because they cause tissue inside the phagosome, there damage are receptors triggering the ➔​ e.g. splinter in fingernail inflammatory pathway. exhibits signs of inflammation ​ Toll-like Receptors (TLRs) - well ​ IMMUNE REACTIONS - these are known receptor family for hypersensitivity reactions in which recognition of foreign bodies. the immune system damages the ➔​ e.g. recognize splinters individual's own tissue (self vs non ​ NOD-like Receptors (NLRs) - self) cytosolic-receptors for cell damage  ➔​ e.g. recognize DAMPS permeability causing (necrosis) leukocytes as well as the liquid ➔​ Recognizes inflammation or component of the blood infection (plasma) to leak out of the blood vessel. ACUTE INFLAMMATION ➔​ When plasma leaks out, it ​ Immediate response of the takes proteins together with it. tissues, blood vessels in injurious ➔​ Clinical importance: Fluid may stimuli. come from pathologic process ​ It has 3 major components: ​ TRANSUDATE - extravascular 1. Dilation of small blood vessels - fluid with low protein concentration increase blood flow ➔​ Clinical importance: Fluid may ➔​ Dilates in order to bring come from pathologic process leukocytes / mediators of Sample case: inflammation into the site. Tumor cells in the body can 2. Increased permeability of cause fluid buildup in a cavity microvasculature - enabling plasma e.g. lungs, may produce proteins and molecules to leave the transudate circulation (diapedesis) 3. Emigration of leukocytes from Examination of the microcirculation - accumulation in the extravascular fluid revealed a focus of injury, their activation to eliminate pleural effusion. This gives the the offending agent. impression that the pathologic ➔​ Leukocytes will leave and process that causes the recruit effusion is a malignancy transudate. ACUTE INFLAMMATION: BLOOD ​ EDEMA (manas) - excess fluid in VESSELS the extravascular space ​ Changes in the flow of blood, ​ PUS (nana) - purulent exudate permeability of vessels - allow the containing leukocytes, debris of movement of plasma proteins and dead cells, microbes leukocytes out of circulation and ➔​ Collection of macrophages, into the site of injury. leukocytes, bacteria ➔​ Blood vessels are not ​ VASODILATION - induced by continuous tubes; they have many mediators, notably fenestrations because they are histamine, involves the arterioles made up of endothelial cells. In first then leads to opening of new response to inflammation, capillaries - increased local blood fenestrations will increase in flow - erythema (rubor), calor size so leukocytes can go (heat). outside of the blood vessel. ➔​ Vasodilation = increased blood ​ DIAPEDESIS - movement of flow = redness (rubor) and heat leukocytes in between endothelial (calor) cells ​ It is followed by increase in ​ EXUDATE - extravascular fluid permeability of the blood vessels - with high protein concentration outpouring of protein-rich fluid into ➔​ Because of inflammation, the extravascular space - tumor there is an increase in vascular (swelling), dolor (pain).  ➔​ Increase in permeability of the blood vessels = extravasation ACUTE INFLAMMATION: LEUKOCYTE of fluid (transudate, exudate) = ADHESION swelling (tumor). ​ When there is stasis of blood in the ➔​ Swelling will compress blood blood vessel, leukocytes are vessels and nerves on the site pushed on the walls of the causing pain (dolor). endothelium - MARGINATION ➔​ Compression will cause ➔​ Laminar blood flow - fastest numbness to the area (functio flow in the center ; other laesa) components on the margin ​ Results in the slow velocity of ➔​ Inflammation - leukocytes are blood flow in the area, increased marginated w/c enables them viscosity, engorgement of blood to interact with the blood vessel vessels - stasis walls. ➔​ Slow down = increased blood ​ Sense signals from the viscosity ; stasis (slow blood endothelium, leukocytes starts flow) rolling (because of stasis) then they will recognize adhesion molecules to be able to attach to the endothelium ➔​ Why do leukocytes need to adhere? So they can move outside of the blood vessel ​ SELECTIN - mediates initial rolling (stopper). Three types: L-selectin (expressed by leukocytes). E-selectin (expressed by endothelium, P-selectin (expressed ➔​ Normal: continuous, streamline by platelets). blood flow ​ The expression of selectins and ➔​ Inflammation: Increased their ligands is regulated by permeability of blood vessel, cytokines in response to infection increased blood flow, stasis to and injury. give time to leukocytes to ​ INTEGRIN - slows down the rolling adhere to the endothelial cells and gives them more opportunity and eventually go out of the to bind firmly in the endothelium blood vessel via diapedesis (ICAM-1 Intracellular Adhesion Molecule) ACUTE INFLAMMATION: LEUKOCYTE RECRUITMENT ➔​ Leukocyte, once adhered, will go out of the blood vessel via 😭 diapedesis with the aid of 😭 Sequential smth incomplete omg 1.​ Increased PECAM-1 2.​ 😭 3.​ ➔​ After the leukocyte adheres and 4.​ establish smth smth omg 😭 5.​ ➔​ mediated by PECAM1 smth smth  the cell and localization of myosin filaments at the back - allows the leukocyte to extend filopodia that pull back the cell in direction of extension ➔​ Actin will contract– there is cytoplasmic movement in the leukocyte ➔​ Filopodia - cytoplasmic extensions of leukocytes ➔​ Because of the chemoattractants, it causes configurational change in the cell of the leukocyte, enabling it to track down and follow the ACUTE INFLAMMATION: CHEMOTAXIS microorganism ​ When the leukocyte migrates from the vascular space to the tissue, they need to follow the ➔​ Arachidonic acid - product of microorganism to kill - chemotaxis the degradation of the lipids in ➔​ chemo - chemical ; taxis - the cell. It is what causes pain movement in injuries. ➔​ Leukocytes can detect ➔​ Injury - break of the cell microorganism because of its membrane will produce chemical trace arachidonic acid. ​ It will require ➔​ It is a fatty acid chain that CHEMOATTRACTANTS - spans more than 20 carbon EXOGENOUS, ENDOGENOUS: long, an eicosanoid. (1) Cytokines (IL-8), (2) ➔​ This acid will either go into the Components of the complement cyclooxygenase pathway or pathway (C5a), (3) Arachidonic lipoxygenase pathway. Acid metabolites (Leukotriene B4). ➔​ Cyclooxygenase pathway - ➔​ Cytokines - chemical cyclo = cyclic structure messengers released by many (arachidonic acid → cells in the body prostacyclin prostaglandin ➔​ NSAIDs MoA includes blocking ➔​ NSAIDs blocks arachidonic acid pathway cyclooxygenase pathway (COX because they produce inhibitors) prostaglandins and ➔​ Can be either COX-1 or COX-2 leukotrienes which are (specific, non-specific) mediators of pain ➔​ Specific inhibitors(?) - e.g. ➔​ NSAIDs are mostly analgesics celecoxib ​ These agents will bind to specific ➔​ Paracetamol - not an NSAID ; GPCR (G protein-coupled weak analgesic ; antipyretic receptors) which will induce (for fever) cellular mechanisms and will result ➔​ After blocking COX pathway, in the polymerization of actin there will be no pain molecules at the leading edge of  ➔​ NSAIDs are called analgesics ; ➔​ Macrophages has mannose Greek Ana (to eliminate) and (sugar) receptor, recognizing algos (pain). bacteria ➔​ Why do phagocytic cells not eat up our cells? Mammalian cells (glycoprotein, glycolipid) have different composition– N-acetylgalactosamine which are not recognized by macrophages. 2.​ Engulfment, with subsequent ➔​ A. Acute inflammation formation of a phagocytic vacuole Mediators: Neutrophils - the ​ Engulfment - after recognition fastest phagocytic cells that of receptions, extensions of the can go to the site of cytoplasm flow around it, and inflammation. plasma membrane pinches off ➔​ Have a short lifespan. If to form an intracellular vesicle inflammation turns chronic, which will fuse to a lysosome neutrophils will be replaced by (phagolysosome) macrophages. ➔​ Phagosome cannot digest ➔​ Tissue undergoing alone– it has to bind with a inflammation has many lysosome (HCl) to form a neutrophils: ACUTE phagolysosome in order to ➔​ Tissue undergoing digest the organism inflammation has many macrophages: CHRONIC 3.​ Killing and degradation ​ Inflammation declines after the ACUTE INFLAMMATION: offending agent is removed: the PHAGOCYTOSIS AND CLEARANCE OF mediators of inflammation only AGENT exist as long as there is 1.​ Recognition and attachment of the inflammation. particle to be ingested by the ➔​ Terminate inflammation. Body leukocyte. should not be in a prolonged ​ Macrophage mannose inflammatory state. receptor - binds to a terminal ​ Neutrophils have short half-lives: mannose and fucose found on they only exist for so long microbial cell walls. ​ As inflammation develops, the Mammalian glycoprotein and process itself triggers a variety of glycolipids contain terminal stop signals that actively terminate sialic acid or the reaction. N-acetylgalactosamine - ​ This termination includes switch receptors only recognize type of arachidonic acid bacterial components. metabolites, anti-inflammatory ➔​ Recognition of molecule cytokines, etc. ➔​ Bacterial cell wall has sugar (mannose and ketose) ​ Marked by the exudation of cell poor fluid into spaces created by injury or inflammation.  ​ The fluid does not contain microbes or large numbers of leukocytes. ​ In body cavities, the fluid may be derived from the plasma (as a result of increased vascular permeability) ➔​ genetic mutation last topic prelims SERIOSA 01/27/2025 ➔​ Another ex. Pericardial effusion MORPHOLOGIC PATTERNS: SEROUS ➔​ These are pathologic INFLAMMATION processes produced in an inflammatory disease. ​ Marked by the exudation of cell poor fluid into spaces created by cell injury MORPHOLOGIC PATTERNS: or into body cavities lined by the FIBRINOUS INFLAMMATION peritoneum, pleura, or pericardium. ➔​ Formation of fibrin material ➔​ Called as serous inflammation. ➔​ Fibrin - coagulation of If inside the body cavities, it is something that forms scar called effusions. ​ Develops when the vascular leaks are ➔​ e.g. fluid in pleural cavity large or there is a local procoagulant (lungs) = pleural effusion stimulus (e.g caused by cancer cells). ​ The fluid does not contain microbes or ➔​ Stimulates fibroblasts to large numbers of leukocytes. produce fibrinous material ➔​ Reason why it's called ​ A fibrinous exudate is characteristic of “serous”. inflammation in lining of body cavities ​ In body cavities, the fluid may be such as the meninges, pericardium. derived from the plasma (as a result of ➔​ Meninges in the brain (inner to 👍 increased vascular permeability). outer): Pia mater - adherent to the 👍 ➔​ Clinical significance of serous brain inflammation: Arachnoid - where CSF 👍 comes from Serous, are usually formed Dura mater from bacteria, or because of ​ Histologically, fibrin appears as an malignant processes. eosinophilic meshwork of threads or sometimes as an amorphous e.g. pleural effusion which may coagulum. be caused by pneumonia or TB ➔​ “eosinophilic” because its a (secondary pleural effusion). protein ➔​ Fibrin threads / tissues entangling each other, forming fibrinous exudate ​ Fibrinous exudates may be removed through fibrinolysis. If not, over time, it will stimulate the ingrowth of  fibroblasts and blood vessels forming produced by the sloughing of scar tissue. inflamed necrotic tissue. ➔​ Fibrinous exudation is a ​ Occurs when tissue necrosis and precursor to scar formation resultant inflammation exist on or near surface epithelium or skin. ​ mucosa in the mouth stomach, intestines, GIT ➔​ E.g. singaw / aphthous sores ​ Skin and subcutaneous tissue of the lower extremities in the individuals ➔​ Usually caused by malignant with disorders that predispose to processes e.g. cancer vascular insufficiency such as diabetes, sickle cell anemia, MORPHOLOGIC PATTERNS: peripheral vascular disease can PURULENT INFLAMMATION develop ulcerations. ​ Characterized by the production of ➔​ In diabetic patients, if sugar pus, an exudate consisting of attaches to the nerve and neutrophils, the liquefied debris of vessels [because they are necrotic cells, edema fluid proteins], it can be destroyed. ➔​ Pus = cells, microorganisms ​ The most frequent cause of purulent When the nerve is destroyed, inflammation is infection with bacteria sensation will be lost at the that cause liquefactive necrosis such lower extremities (L.E.). When as streptococcus (streptococcus a blood vessel is destroyed, pyogenes); they are referred to as blood flow will be poor at the pyogenic bacteria. L.E. which would lead to ➔​ Pyogenic = produces pus deficient blood flow. Ischemia ➔​ S. pyogenes causes sore in the L.E. would lead to throat necrosis of the surface ​ ABSCESSES - localized collection of epithelium or skin = pus. They have a central liquefied ulcerations. region composed of necrotic ➔​ E.g. diabetic ulcers leukocytes and tissue cells. ​ There is intense polymorphonuclear ➔​ Sometimes accumulate on infiltration and vascular dilation in the body cavities margins of defect. ​ With chronicity, the margins and base of the ulcer develop fibroblastic proliferation, scarring, as well as accumulation of lymphocytes, macrophages, plasma cells. MORPHOLOGIC PATTERNS: ULCERS ➔​ Most common ​ Local defect, or excavation of the surface of an organ or tissue that is  ➔​ B. There is discontinuity / type IV hypersensitivity reaction or snapping off of the mucosal delayed hypersensitivity reactions. surface ➔​ E.g. TB caused by ➔​ What we don’t want to happen Mycobacteria with ulcerations: perforations of ➔​ Difficult for macrophages to hollow organs digest and degrade the ➔​ E.g. If duodenum is perforated bacteria because it has wax or because of ulceration, contents lipid around it. will leak into the peritoneal ➔​ These organism evoke a cavity which will cause delayed-type of hypersensitivity infection (peritonitis). reaction (Type 4) 2.​ HYPERSENSITIVITY DISEASES - ​ During the acute stage, there is caused by excessive or intense polymorphonuclear inappropriate activation of the infiltration and vascular dilation in immune system leads to the margins of the defect. autoimmune conditions. In these ​ With chronicity, the margins and diseases, autoantigens evolve a base of the ulcer develop self- perpetuating immune reaction fibroblastic proliferation, scarring, that results in chronic tissue as well as the accumulation of damage and inflammation (e.g. lymphocytes, macrophages, and rheumatoid arthritis, multiple plasma cells. sclerosis). ➔​ Hypersensitivity vs Allergy CHRONIC INFLAMMATION ➔​ Allergic reaction: Stimulus is a ➔​ macrophages biological component (e.g. ​ A response of prolonged duration protein, lipid, a part of a living which inflammation tissue injury band organism, plant) attempts to repair coexist in varying ➔​ Hypersensitivity reactions: combinations. inanimate / non-living, ​ It may follow acute injury or it may chemicals begin as an insidious, low grade, ➔​ e.g. hypersensitivity with soap - smoldering response without any irritant contact dermatitis manifestations of preceding acute reactions. ➔​ ANTIGEN vs ANTIBODY ➔​ Can originate from an acute ➔​ Antigen: evokes / stimulates inflammation or its a the immune system to produce slowly-developing inflammation antibodies that becomes chronic over ➔​ Any part of the microorganism / time. virus (flagellum. Cell wall, spike protein) when recognized by CHRONIC INFLAMMATION: CAUSE the body will produce 1.​ PERSISTENT INFECTIONS - antibodies against it so that difficult to eradicate microorganism is easily microorganisms Mycobacteria, degraded by the body. certain viruses, fungi, parasites. ➔​ Antigen-antibody increases in They can evoke a certain type of H.S. rxn that it becomes hypersensitivity reaction called complexes w/c can destroy body tissues  ➔​ In systemic lupus -​ ATTEMPTS OF HEALING - sites erythematosus have lupus of injury are replaced by nephritis. Antigen-antibody connective tissue (scar) complex destroys the kidney accomplished by angiogenesis tissues. (proliferation of blood vessels and 3.​ PROLONGED EXPOSURE TO tissue). TOXINS - either exogenous or ➔​ On cases of TB, the lungs from endogenous. Example: exposure a scar after it heals to silica, when inhaled for prolonged periods, results in inflammatory lung disease called silicosis. ➔​ Lungs cannot remove silica. Fibroblasts will form tissues / scarring around it. ➔​ Granuloma - accumulation of -​ Endogenous - macrophages and m. Atherosclerosis - chronic tuberculosis inflammatory process of the CHRONIC INFLAMMATION: CELLS arterial wall induced by AND MEDIATORS excessive production and ​ The dominant cells in most chronic tissue deposition of inflammatory reactions are exogenous cholesterol and macrophages – they secrete other lipids. cytokines and growth factors that act ➔​ Buildup of fat in blood vessels, on various cells, destroying foreign narrowing it and causing invaders and tissues, activating other ischemia. Poor perfusion of cells notably T lymphocytes. blood in the heart which leads ➔​ Cytokines - chemical to myocardial infarction and messengers that signals an necrosis. ongoing infection in the area ➔​ T-lymphocytes = T-helper cells ➔​ Toxins: Fluoride, alcohol ; T-killer cells (volatile) ➔​ T-helper cells tell the body or ➔​ Can be carcinogenic or cause other cells of ongoing molecule fluctuations over long inflammation ; cells destroyed periods of time by HIV ​ Macrophages are derived from CHRONIC INFLAMMATION: hematopoietic stem cells in the bone MORPHOLOGICAL FEATURES marrow in postnatal life and from progenitors in the embryonic yolk sac -​ Infiltration or mononuclear cells and fetal lives. including macrophages, ➔​ Monocyte before turning into lymphocytes plasma cells macrophages ➔​ Polymorphonuclear cells: ​ MONOCYTE - circulating cells of neutrophils, basophils (more macrophage (when inside the blood than 1 nucleus) vessel) -​ TISSUE DESTRUCTION - induced ➔​ When monocyte goes out of by persistent offending agent or by the blood vessel to respond to the inflammatory cells  an inflammation, it activates to present antigen on their cell become a MACROPHAGE surface ➔​ It activates in order to be ➔​ Once they phagocytize capable of phagocytosis - the microorganism, it will cut up the most important function of cells parts and present it on their cell of inflammation surface so that other ​ KUPFFER CELLS - liver, SINUS inflammatory cells can HISTIOCYTES - spleen and lymph recognize the invader inside nodes the body. MICROGLIA - CNS, ➔​ Once T-lymphocytes recognize ALVEOLAR MACROPHAGE/DUST the antigen presented by the CELLS - lungs antigen-presenting cell, they TISSUE MACROPHAGES - tissue can become another ​ The product of activated macrophage T-lymphocyte. They can also eliminates injurious agents such as proliferate in response to the microbes and initiates the process of activation of the repair, but are also responsible for antigen-presenting cell or they much of the tissue injury in chronic can produce cytokines w/c tells inflammation. other immune cells that there is an inflammation ongoing. ➔​ If it's a B-lymphocyte, it can transform into another B-lymphocyte. It can secrete cytokine or become a plasma cell which eventually becomes antibodies upon activation. ➔​ Antigen-presenting cells can activate B-lymphocytes to become antibodies. ➔​ B lymphocyte -> plasma cell -> antibodies upon activation Anong hirono daw trip mo CHRONIC INFLAMMATION: MACROPHAGE ​ Initiate the process of tissue repair and CHRONIC INFLAMMATION: PATHWAY are involved in scar formation and OF ACTIVATION fibrosis. ​ They secrete mediations of ​ CLASSICAL - induced by microbial inflammation such as cytokines (TNF, products such as endotoxin which IL-1) and eicosanoids. engage TLRs and other sensors; by T ​ They display antigens to T cell derived signals, importantly the lymphocytes and respond to signals cytokine (FN-y). The main role of the from T cells, thus setting up a macrophages in host defense is to feedback loop that is essential for destroy microbes and promote the defense against many microbes by inflammatory response. cell-mediated immune responses. ➔​ Microorganism itself bind to the ➔​ Macrophage cell -antigen-presenting cell - ➔​ Linear ​ ALTERNATIVE - induced by cytokines subcutaneous tissue, it other than IFN-y such as IL-4 and reaches the connective tissue IL-13, produced by T-lymphocytes and beneath. The damage is so other cells. severe to the tissue and the ➔​ Products of activation of extracellular matrix that it microorganism in a cell that cannot be patched up by produces cytokine regeneration. ➔​ Thus, the body will form a scar. CELL AND TISSUE REGENERATION ​ Regeneration Involves cell proliferation, which is driven by growth factors and is critically dependent on the integrity of the 02/03/2025 ECM, and by the development of mature calls from tissue stem cells. case study ➔​ Importante sa scar infographic poster a4 formation/wound healing or peer evaluation tissue repair ang growth factors ➔​ Your growth factors, they are TISSUE REPAIR (HEALING) the ones that will stimulate the growth of tissues , growth of TISSUE REPAIR the epithelium, and the growth ​ Also caller healing refers to the of the cells. restoration of tissue architecture ➔​ If no growth factors, hindi mag and function of an injury. h-heal. Will not patch up, hindi ​ It includes two main mechanisms: magkakaroon ng scar. Regeneration - complete restoration of the damaged tissue ​ Growth factors are produced by to its original state. calls near the site of damage ➔​ If the damage is superficial MACROPHAGES - activated by (mababaw) the body could tissue injury. undergo regeneration, and in ➔​ MACROPHAGE - Main cell in the process of regeneration chronic inflammation there is complete restoration of ➔​ Besides the fact that the the architecture of the cells of MACROPHAGES respond to the tissues. the site of injury, they’re also ➔​ Mild superficial injury the one that initiates or ​ Connective Tissue Deposition secretes the growth factor (scar formation) - if the injured needed for the repair of the tissues are incapable of tissue. regeneration, repair occurs by ​ These growth factors activate laying down connective (fibrous) signaling pathways that stimulate tissue which may result in scarring. DNA replication while also ➔​ There is a severe injury that fostering changes in metabolism happened to the tissue or to that promote biosynthesis of other the organ. Image The cellular components that are laceration extends up to the  needed to produce daughter cells - with connective tissue, leading to cell division. the formation of a scar, ​ Scar formation is a response that ➔​ The macrophages initiate the patches rather than restores the secretion of these growth tissue. factors and the growth factors ➔​ Analogy: Pagsusulsi. A portion in turn allow the cell of the fabric will be taken and proliferation–regeneration and used to cover the hole. A the deposition of the different PATCH, which is what happens components of the extracellular during the scar formation. matrix needed for scar ➔​ In the event of an injury Ex. formation. → So lahat ng ‘yon, “Nagkalmutan kayo ng jowa ang trigger niya is the mo, pagkakalmot niya sa’yo MACROPHAGE. nagkaroon ka ng sugat sa braso” Now, the tissue of that wound will bleed, and then, in response to bleeding, your body will create a hemostatic plug, the wound will be patched using PLATELETS. ➔​ Platelets will form platelet clog on that area of wound, it will clog whatever was damaged, then after a while it will dry. ➔​ If it dries, ESCHAR (Langib / Scab) will form. ➔​ Underneath the Eschar, there will be collagen deposition– magkakaroon ng formation of scar until such time na mawala yung scab/langib and the marks of the scar. However, if inspected closely, it will be seen visibly. ➔​ It will not be visible from afar if the wound isn’t very big. But if it is big, the wound will be very visible especially if the individual is keloidal. ​ Repair by connective tissue deposition consists of sequential processes that follow tissue injury. Within minutes after injury, a hemostatic plug composed of CONNECTIVE TISSUE DEPOSITION hemostatic plug composed of ​ If repair cannot be accomplished platelets is formed, which stops by regeneration alone, it occurs by bleeding and provides **scaffold?? replacement of the injured cells For the deposition of fibrin.  ➔​ They patched up the epithelium ➔​ If the repair cannot be ➔​ Sila nag f-fill up ng nawalang accomplished by regeneration epithelium ○​ Endothelial cells - proliferate to form new blood vessels–angiogenesis ➔​ Nakikita sa blood vessels ➔​ They are the cells that made up your blood vessels. ➔​ Why do we need endothelial cells? ◆​ To form new blood vessels (process of angiogenesis) ➔​ Why do we need new blood vessels? ◆​ Because we need blood supply, to the area or the tissue of damage. ◆​ Blood supply will bring the nutrients (important for the formation of the scar) ○​ Fibroblasts - proliferate and migrate to the site of injury to lay down collagen fibers ➔​ They lay down the collagen fibers ➔​ The collagen fibers are like the thread. They would strengthen and patched up missing or filler SCAR FORMATION sila sa area kung saan nawala ​ INFLAMMATION - inflammatory yung tissue. Eventually, those cascade, eliminating to the collagen fibers will build up offending agent, resolution of the cellular matrix, tissue, laman inflammatory pathway and everything. ​ CELL PROLIFERATION - several ➔​ REMEMBER these THREE cell types, including epithelial cells, cells. endothelial cells, and other vascular cells, fibroblasts, proliferate and migrate to close the ANGIOGENESIS - The process of new wound blood vessel development from existing ○​ epithelial cells - respond blood vessels to locally produced growth ➔​ ANGIOGENESIS is different factors and migrates over from vasculogenesis. wound to cover it up Vasculogenesis is the  formation of new blood vessels. In Angiogenesis on the other hand, one blood vessel will branch off to form another branch of the blood vessel, it’s like franchising. ➔​ The terms angiogenesis and vasculogenesis are different terms. ➔​ In angiogenesis, there is growth. There is an extension of a blood vessel. When there is growth, you have to have GROWTH FACTORS. ➔​ Specific growth factors needed for ANGIOGENESIS ◆​ Vascular Endothelial Growth Factor (VEGF) ​ Vasodilation in response to nitric oxide and increased permeability induced by vascular endothelial growth factor (VEGF) - VEGF stimulate the production of NO which in turn vasodilates blood vessels. ​ Separation of pericytes from the ➔​ The endothelial cells will abluminal surface and breakdown proliferate. The pericytes will of the basement membrane to break off, they will separate on allow formation of vessel sprout. the site or at the point of angiogenesis. The endothelial cells will multiply, tapos nag-break yung pericytes. It will continue multiplying until such time that they will form a new blood vessel. It elongates. From there, it can connect to another blood vessel or become an independent blood vessel. Then, you will have a new blood vessel. ➔​ ANGIOGENESIS is important in the delivery of essential nutrients in the site of injury. ➔​ How will there be a good blood supply in that area? ANGIOGENESIS. → Also the  reason why some researchers missing space. That’s why on focus on antiangiogenesis if their proliferation, there’s so they want to remove or to kill much collagen fibers. tumors or cancer cells. This is ➔​ There are some procedures in because cancer cells have the dermatology that wounds the ability to create or promote skin to promote collagen angiogenesis around them so formation. Ex: Diamond peel, that they would have a good uses microneedles to wound blood supply. the skin in order to promote ➔​ So if you kill, or disallow the growth, promotes proliferation tumor cells’ formation of new of collagen fibers. blood vessels, the cancer cells ➔​ Collagen supplements and will die. drinks have no assurance that they actually go to the skin GRANULATION TISSUE because collagen are tertiary ➔​ Precursor of the scar. proteins, when they are ​ Migration and proliferation of absorbed in the body they are fibroblasts and deposition of loose degraded into amino acids. connective tissue, vessels and Those amino acids ‘di natin integrated interspersed alam kung saan sila pupunta, it mononuclear leukocytes - depends on where it needs the granulation tissue. materials, if it’s not in the skin, ○​ Mononuclear leukocytes then it won’t go to the skin (Macrophage & ◆​ Alternative: Eat glow foods Lymphocytes) Ex. Carbohydrates that give energy, Vegetables, Fruits, ​ Histologically - proliferation of Vitamins fibroblasts and thin-walled, delicate capillaries (angiogenesis) in a loose ECM, often with admixed inflammatory cells, mainly macrophages. ➔​ Thin-walled because they recently went through angiogenesis (kaka-angiogenesis palang nila, kaka-form palang) ➔​ ON HISTOLOGICAL PREPARATION you can see fibroblast. Then there’s a few blood vessels, (How to tell: because there are red blood cells inside. Thin-walled) The violet and the blue fibers seen are the collagen fibers, they are important because they lay down the scar tissue that is visible and patch up the  ➔​ TGF-b - Tissue Growth Factor beta ➔​ These factors are all derived from activated macrophages.All of them came from macrophages. ​ TGF-b is the most important cytokine for the synthesis and deposition of connective tissue proteins REMODELLING OF CONNECTIVE TISSUE - the outcome of the repair process is influenced by a balance between synthesis and degradation of ECM proteins ​ Degradation of collagens and other ECM components is accomplished by a family of matrix metalloproteinases (MMPs) so called because they are dependent of metal ions (e.g. zinc) - they cleave fibrillar collagen, gelatinases, etc. ➔​ After the scar or tissue is laid down on the site of injury, it is not made perfectly. That’s why there is remodelling–they DEPOSITION OF CONNECTIVE TISSUE shape the scar formation. - granulation tissue is progressively ➔​ Remodelling needs enzymes replaced by deposition of collagen. because these enzymes ​ The laying down of connective degrade the excess tissues, tissue occurs in two steps: collagen fibers, and migration and proliferation of extracellular matrix so that the fibroblasts into the site of injury, scar tissue will at least look and deposition of ECM proteins aesthetically pleasing despite produced by these cells being visibly obvious to the ​ The process is orchestrated by eye. locally produced cytokines and ➔​ These enzymes are called: growth factors including PDGF, ◆​ Matrix Metalloproteinases FGF-2, TGF-b, which are all (MMPs) – They shape the derived from activated extracellular matrix, they macrophages degrade the excess. ➔​ PDGF - Platelet Derived Growth Factors ➔​ FGF - Fibroblast Growth Factors FACTORS THAT INFLUENCE TISSUE REPAIR ​ INFECTION - clinically one of the there is no inflammation→ most important causes of delayed there is no tissue repair. healing ➔​ Steroids also inhibit tissue ➔​ If a wound is infected, it won’t growth factors, without those heal. It will not promote healing growth factors, there is no because the infection will not wound healing. promote the growth of the ​ MECHANICAL FACTORS - such tissue. Because the tissue as increased local pressure of produced by the body will be torsion may cause wounds to pull degraded? Sisirain rin ng apart of dehisce infection. ➔​ Ex: Kinukutkot yung sugat ➔​ The first thing to do when a ➔​ Daming hugot ni sir amp wound is induced to the patient ​ POOR PERFUSION - Peripheral for instance, in tooth extraction vascular disease, arteriosclerosis, a wound will be formed, make diabetes, ischemia sure that the patient will ​ FOREIGN BODIES - fragments of receive antibiotics to prevent steel, glass, bone, impede healing infection Ex. Clindamycin. by perpetuating chronic ​ DIABETES - Compromises tissue inflammation repair for many reasons and is one ➔​ The reason why the knot of the of the most important systemic sutures nakalagay sa gilid is causes of abnormal wound healing because it can impede the ➔​ Impedes wound healing wound. because an individual’s sugar will cause destruction to the HEALING OF SKIN WOUNDS proteins. If a sugar gets ​ By the end of the first month, the attached to a protein, it may scar comprises a cellular result in the degradation of the connective tissue largely devoid of protein. And if it moves to the inflammatory cells and covered by tissue or blood vessels, it can an essentially normal epidermis. destroy either, resulting in no proper or very slow wound HEALING BY FIRST INTENTION healing. ​ EX. ➔​ The patient’s sugar should be ➔​ “If the wound is superficial, controlled so there would be hindi siya masyadong malala efficient wound healing. and hindi siya masyadong ​ NUTRITIONAL STATUS - malaki, then the healing is by Profound effects n repair; protein first intent. Magclclose and deficiency and vit C deficiency - magheheal siya ng kusa.” collagen synthesis ​ GLUCOCORTICOIDS (STEROIDS) - Have HEALING BY SECOND INTENT anti-inflammatory effects; they ​ In large wound deficits, the fibrin weaken the scar by inhibiting clot is larger, there is more exudate TGF-b production and diminished and necrotic debris in the wounded fibrosis area. Inflammation is more intense. ➔​ Inhibit inflammatory cells, ​ Much larger amounts of without inflammatory cells granulation tissue are formed to fill  a bigger gap caused by the larger ​ DIABETIC ULCERS - they affect area of deficit the lower extremities PRESSURE. ​ Wound contraction — an important ➔​ The first management in feature in healing by secondary diabetic ulcers is to control the union, helps close the wound by sugar so that the wound will decreasing the gap, decreasing the heal properly. wound surface area. ​ ULCERS - or bedsores, areas of ➔​ Needs suturing, to appose the the skin ulceration and necrosis wound edges together and to underlying tissues caused by prevent the gaping? Bleeding? prolonged compression of tissues especially when the wound is against a bone. near high tension (belly, legs, ➔​ Result from prolonged forehead) mechanical pressure on the area of bony surfaces. Ex. ABNORMALITIES IN TISSUE REPAIR Backside, sacrum, elbow. If the ​ VENOUS LEG ULCERS - these patients are immobilized or ulcers fail to heal because of poor bedridden for a long time, they delivery of oxygen to the site of can develop pressure ulcers. ulcer *severe varicose).......... ​ HYPERTROPHIC SCAR - ‘ Blackish-bluish color excessive-scarring cibtaubedbin ➔​ The defect is in the venous the area of injury. circulation. There is poor blood ➔​ The wound developed supply in the area, thus an hypertrophy (increase in cell ulceration was formed. It may size), but the scar tissue be because the vein is clogged remained on the site of injury. (may bara) or in diabetic ​ KELOIDAL SCAR - excessive people. scarring extending beyond the ➔​ Blackish-bluish in color due to wound healing site the deposition of the iron ➔​ It extends beyond the site of treatment, hemosiderin. injury. ​ ARTERIAL ULCERS ‘ - develop in individuals with atherosclerosis of peripheral arteries. The ischemia results in atrophy and then necrosis of the skin and underlying tissues - can be painful. Red color ➔​ Nababara ang arteries. There is atherosclerosis or fat deposition in the arteries that causes poor blood supply. ➔​ Remember, if there’s poor blood supply, it will most likely lead to ulceration. ➔​ This type of ulcer is painful because it’s near nerves. So if destroyed, the nerves will be exposed, causing pain. ➔​ Red in color. Bring white folder :)