WVSOM renewal and repair lec 5&6 pathology
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| What does the renewal and repair of tissue begin with? | cell/tissue loss, process of renewal from natural cell loss differs from cell loss due to injury
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| What are some responses to the loss of cell/tissue? | cell migration to site of loss/injury, cell proliferation, reorganization, deposition, and remodeling of extracellular matrix (ECM) components
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| What causes cell loss? | can be natural or pathologic
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| What are the different types of cell/tissue loss? | natural and pathologic
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| What are the natural cell/tissue cell loss? | sloughed epithelia (skin from any surface of the body, mucosa), usually a balance of proliferation and apoptosis, senescence, or mechanical loss
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| What are the pathologic cell/tissue loss and what do you lose? | injury/inflammatory destruction, loss of parenchymal cells (epithelial cells that form a function), loss of stromal cells (mesenchymal, fibroblasts) that support function
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| What is the function of stroma cells? | support function
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| What is the function of parenchymal cells? | perform the function of the tissue
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| How can repair after injury occur? | by regeneration of cells or tissues that restores normal tissue structure, or by healing which leads to the formation of a scar.
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| What may cause massive fibrosis? | chronic inflammation
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| What is included in all loose cells that replenish? | Hair, Dermis, epidermis, sebaceous gland, hair follicle bulge, epidermal stem cell
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| In the center of the hepatic globule is what? | central vein
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| What delivers nutrients from the gut to the liver? | The portal vein
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| What can happen when there is injury to cells within the liver? | When the hepatocytes proliferate to repopulate what has been lost they do along this reticular fibers, If the reticular fibers have been lost you end up with just reticular fibers or just fibrosis
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| When ever you have inflammation what is the result? | destroys everything
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| The cells that are involved in the repair process are what? | inflammatory cells, parenchymal cells, fibroblasts and other stromal cells, and endotheilial cells
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| What does the inflammatory cells do for the repair process? | macrophages remove damaged or degenerated cells/tissue and prevent infection
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| What does the parenchymal cells do for the repair process? | could include stem cells to repopulate tissue with primary functional cell type
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| What does the fibroblasts and other stromal cells do for the repair process? | fibrosis is deposition of collagen and other ECM in process of repair, this provide structural integrity to damaged tissue
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| What does the endothelial cells do for the repair process? | think angiogenesis, renew blood flow that is vital for repair process
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| What is Angiogenesis? | the growing of new blood flow vital for repair process
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| What removes the dead or dying cells? | inflammatory cells
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| Which collagen type is present in early wounds and hollow structures? | Collagen type 3
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| Which collagen is more globular, type 4 usually forms the basemement membrane? | Non Fibrilar collagen
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| What break down elastins? | Elastases
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| What are the fibrous structural proteins? | collagens
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| Which collagen consists of type 1,2,3,5,6? | fibrilar
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| When is type 1 collagen present and describe its character? | present in late wounds, strong and rigid
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| What collagen type makes up the basement membrane? | type 4 collagen
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| What type of tissue does the liver falls into? | quiescent tissues
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| What are quiescent tissues? | They can easily proliferate if they need to
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| What are labile tissues? | continuously dividing tissues like surface epithelium, blood cells progenitors
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| What are stabile tissues? | quiescent tissues, stay in Go with limited ability to proliferate until needed then stimulated to enter G1 of cell cycle such as perenchyma of many solid organs and fibroblasts, endothelial cells
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| What are permanent, post-mitotic tissues? | terminally differentiated tissues, they don’t divide to replace what is lost such as cardiac myocytes and neurons
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| If you have a superficial injury to the skin what is involved and what is the goal? | epidermis and superficial dermis, minimal granulation tissue formation, goal to renew the epithelium
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| If you have a deeper injury to skin and sub-Q tissue what is involved? | more extensive granulation tissue formation with replacement of lost connective tissue, fibrosis scarring, may require help such as sutures and skin grafting
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| What is hemostasis? | fibrinogen forming fibrin which forms scabs or eschar
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| What is the provisional matrix? | temporary ECM; loose (supports cell migration) has type 3 collagen and proteoglycans
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| What is the granulation tissue? | transient, specialized for repair containing type 3 collagen, monocytes, plasma cells, and macrophages, angiogenesis with activation of fibroblasts
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| What is the sequence of wound healing? | hemostasis, inflammation, provisional matrix, granulation tissue, fibroblast proliferation and collagen deposition/ remodeling, re-epithelialization, wound contraction, increase in wound tensile strength
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| What does fibroblast proliferation and collagen deposition/remodeling consist of? | ECM remodeling; action of enzymes to degrade MMPs and deposition of new proteins
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| What is involved in re-epitheliazation? | parenchymal recovery (cell proliferation and migration)
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| What is involved in wound contraction? | myofibroblasts
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| How much of the original strength integrity do you achieve after injury and what type of collagen is used to form the scar? | ~75%, Type1 collagen
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| What is the earliest process of wound healing? | Inflammation is the earliest process but there is a lot of over lap with granulation tissue
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| As the inflammation is still there granulation tissue comes into play and at the end of granulation tissue, what happens next? | you have collagen accumulation and remodeling as well as wound contraction
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| What happens in the early stages of repair in skin? | thrombosis, inflammation, reepitheliazation
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| What happens in the mid stages of repair of skin? | granulation tissue formation and function, contraction
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| What happens in the late stages of repair of skin? | accretion of final tensile strength, remodeling and conformation to stress lines in the skin
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| With a Trichrome stain what color does collagen stain? | blue
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| With the trichrome stain of a mature scar what do you see? | lots of blue with dense collagen with only scattered vascular channels
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| Why do they call it Granulation tissue? | because of the gross appearance it has a granular look to it
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| What are the two major components of granulation tissue? | fibroblasts, myofibroblasts, and macrophage cells and proliferating capillaries
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| What are the fibroblasts and myofibroblasts derived from? | mesenchymal stem cells
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| Where do the new capillaries arise from? | adjacent vessels by division of the lining of endothelial cells by angiogenesis
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| What are pseudopodia? | extensions from endothelial cells that grow toward the wound site
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| At its peak which tissue is the most richly vascularized tissue in the body? | granulation tissue
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| What are the settings in which wound healing does not heal very well? | some of this is determined by location, blood supply, and amount of nature of ECM at site of injury
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| What does the location of the wound determine? | ability of wound to contract, example soft tissue over tibia is thin with poor contraction
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| List some examples of amount and nature of the ECM at site of injury determine: | skin of aged has less collagen and elastin, corticosteroids impair wound healing
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| How does blood supply affect healing? | Greater the blood supply the better the healing
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| What are some causes of impaired blood flow complications? | pressure ulcers, areas affected by atherosclerosis, vericose veins, articular cartilage
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| Does depth of skin and soft tissue damage affect healing? | yes, If you have a real deep wound you are going to destroy more structures and have to repair more
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| What can be a reason for portal hypertension? | you have liver damage, and get regrowth without central veins, If you lack central veins there is no good way to remove the blood and this can lead to portal hypertension
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| What is cholestatic jaundice? | jaundice caused by bile being static in the liver due to the fact of no central vein to remove it from the liver
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| What can lead to contractures? | a deep wound
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| What can lead to cirrhosis of the liver? | fibrosis with continued pernchymal and ECM damage
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| What are hepatocyte nodules? | regrowths of liver tissue that lack central veins; expanding nodules obstruct blood and bile flow which can lead to portal hypertension and cholestatic jaundice
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| Which wound heals more readily and with better results, primary or secondary? | primary
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| What is the result of secondary reaproximation? | have more granular tissue and end up with less dense and weaker tissue, so you have a little bit of depression
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| Why do we use sutures? | to help turn a secondary wound into a primary wound
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| As you go through wound healing from an ulcer what happens? | you get a thin bed of epithelium as that continues you get the re-epitheliazation, and contraction
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| What is the consequence of chronic hepatic injury? | Cirrhosis, the formation of regenerating nodules separated by fibrous bands
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| What happens if injury to the kidney does not significantly damage the framework (ECM)? | leads to renal tubal epithelium regeneration
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| What happens if injury to the kidney damages the framework (ECM)? | renal scarring, chronic glomerulonephritis
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| Where is the regenerative ability of the kidney maximal? | in cortex, less in medulla, and glomeruli do not regenerate
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| Do renal glomeruli regenerate? | NO
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| What does scar tissue in the kidney look like under a microscope? | pink circles like slices of jawbreakers
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| When talking about regeneration of denuded or damaged epithelium in the larynx, trachea, and bronchi what is the outcome? | reversible squamous metaplasia
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| When talking about regeneration of denuded or damaged epithelium in the Alveoli what is the outcome? | type 2 pneumocytes proliferate and differentiate, so you have type 2 changing to type 1 cells
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| If the underlying stroma is damaged in the lung/respiratory tract what does it lead to? | fibrosis, interstitial pneumonia and fibrosis from type 1 collagen
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| When looking at acute pneumonia what do you see under the microscope? | The air spaces are filled with neutraphils but the septa are intact
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| When looking at chronic interstitial inflammation what do you see under the microscope? | you see nodules of lymphocytes, you can see that the septa are thick
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| Which do you have a better chance of healing from, chronic interstitial inflammation or acute pneumonia? | With acute you have pretty good healing in chronic you do not
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| What does a loss of cardiac myocytes result in? | fibrosis
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| If you have patchy loss of cells in the heart what does it lead to? | interstitial fibrosis, ischemic heart disease/cardiomhyopathy
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| If you have diffuse loss of cells in the heart what does it lead to? | myocardial infarction which follows coagulative necrosis and repaired with type 1 collagen
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| What type of tissue does heart cells fall under? | post-mitotic or permanent tissue meaning they do not regenerate
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| What happens if you get an acute inflammation in the heart? | fibrosis tissue
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| If you took a section through a healed myocardial infarct what would you see? | mature fibrosis and disrupted myocardial fibers
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| What type of cells make scar tissue in the nervous system? | Astrocytes = glial cells
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| What type of tissue does neurons fall under? | Post mitotic meaning they lack reliable capacity to proliferate
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| Explain axonal regeneration following trauma/injury for the PNS and CNS? | PNS can elongate (grow) and remake synapses, CNS lack this ability
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| How is scarring accomplished in the CNS and PNS? | CNS scaring is from glial cell proliferation (gliosis), and PNS fibrosis from fibroblasts
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| What is a hypertrophic scar? | excessive scar formation due to excess collagen and poor primary or secondary intent wound healing
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| What is a keloid? | exuberant, disorganized collagen deposition within dermis that extends beyond the anatomic confines of normal structure usually in dark skinned people
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| If you take a slice of a keloid and looked at it under a microscope what would you see? | a crap load of connective tissue in the dermis
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| What is a contracture? | deformity of wound and surrounding structures, common following burns, can produce bowel strictures when in abdomen
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| What areas are prone to pathologic contractures? | areas that show minimal wound contraction, like palms and soles
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| What is pyogenic granuloma? | exuberant overgrowth of granulation tissue, eg. Gingiva of pregnant women
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| What is proud flesh? | granulation tissue extends above the epithelial surface and precludes re-epitheliazation
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| What are desmoids or aggressive fibromatosis? | excessive, persistent fibrosis following injury or surgical incisions within soft tissues
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| Epulis is clinical term for what? | pyogenic granuloma
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