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Chapter 3: Altered Cellular and Tissue Biology Cellular Alterations  Injury to cells and their surrounding environment (called the extracellular matrix) leads to tissue and organ injury  Cells can adapt to physiologic demands or stress to maintain a steady state called homeostasis  Adaptation is a reversible, structural, or functional response both to normal or physiologic conditions  Example: uterus adapts to pregnancy—a normal physiologic process—by enlarging  Example: in adverse condition such as hypertension, myocardial cells are stimulated to enlarge by increased work of pumping and are usually only temporarily successful Cellular Adaptation  Physiologic vs. pathogenic o Atrophy – decrease or shrinkage in cell size and consequently in size of affected organ o Hypertrophy­ increase in size of cells and consequently in the size of the affected organ o Hyperplasia­ increase in number of cells form increased rate of cell division o Dysplasia­ abnormal changes in size, shape, and organization of mature cells o Metaplasia­ reversible replacement of one mature cell type by another, sometimes less differentiated cell type Cellular Injury  Reversible  Irreversible Cellular Injury Mechanisms  Hypoxic injury—single most common cause of cellular injury o Ischemia—reduced blood supply o Anoxia­ total lack of oxygen o Cellular responses  Decrease in ATP, causing failure of sodium­potassium pump and sodium­calcium exchange (allows calcium to enter into the cell, killing the cell)  Cellular swelling  Vacuolation­ is the formation of vacuoles within or adjacent to cells, and, in dermatopathology, often refers to the basal cell­basement membrane zone area. o Reperfusion injury­ restoration of oxygen that results from generation of oxygen free radicals that can cause further cell membrane damage and mitochondrial calcium overload  Chemical injury o Carbon tetrachloride­ now banned, used in industries such as refrigeration and pesticides o Lead—paint, soil, pottery, mining o Carbon monoxide—hypoxic asphyxiation, odorless, colorless, deadly o Ethanol—alcohol intoxication/poisoning o Mercury—fish consumption and dental amalgams o Social or street drugs—heroin, meth, cocaine Unintentional and Intentional Injuries  Blunt force injuries o Application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues o Contusion vs. hematoma  Contusion­ bruise caused by bleeding into skin or underlying tissues  Hematoma­ is a collection of blood in soft tissue o Abrasion – wound or scrape cause by superficial damage to the skin, no deeper than the epidermis o Laceration­ tear or rip in tissue; ragged & irregular with abraded edges caused by blunt trauma  Extreme example is an avulsion where a wide area is pulled away; organ injuries can also become lacerated from blunt force o Fractures­ breakage of bone from blunt force trauma  Sharp injuries o Incised wounds  Longer than it is deep  Straight or jagged with sharp, distinct edges without abrasions  Usually produces significant external bleeding and little internal bleeding  May see superficial incisions in same area called “hesitation marks” o Stab wounds  Penetrating sharp force injury that is deeper than it is long  External bleeding small due to almost immediate tissue pressure over site o Puncture wounds  Made by objects with sharp points but without sharp edges  Prone to infection  Can be deep (stepping on nail) o Chopping wounds  Made by heavy, edged instruments such as hatchets, propeller blades  Produces a combination of sharp and blunt force characteristics Unintentional and Intentional Injuries—Gunshot Wounds  Contact rang entrance wounds occur when gun is held so that the muzzle rests or presses on the skin surface o Searing of edges of wounds from flame/smoke in addition to hole o Wounds is gaping and/or jagged which is called blow back that mirror the imprint of the weapon  Intermediated range entrance wound: surrounded by gunpowder stippling/tattooing that results from fragments of burning or unburned pieces of gunpowder exiting gun barrel and forcibly striking skin Exit Wounds  Shored exit wounds Unintentional and Intentional Injuries  Asphyxia injuries—caused by a failure of cells to receive or use oxygen o Suffocation­ choking asphyxiation o Strangulation – hanging, ligature, and manual strangulation o Chemical asphyxiants – carbon monoxide most common, cyanide, and hydrogen sulfide (sewer gas) o drowning Infectious Injury  Pathogenicity of a microorganism  Disease­producing potential o Invasion and destruction o Toxin/endotoxin production o Production of hypersensitivity reactions Immunologic and Inflammatory Injury  Phagocytic cells  Immune and inflammatory substances o Histamine, antibodies, lymphokines, complement, and proteases  Membrane alterations  WILL DISCUSS DETAILS IN IMMUNE SYSTEM Cellular Death  Necrosis: sum of cellular changes after local cell death and the process of cellular auto­digestion o Coagulative necrosis  Kidneys, heart, and adrenal glands  Protein denaturation  Usually caused by ischemia or infarction caused by chemical injury o Liquefactive necrosis  Ischemic injury to neurons and glial cells of the brain and is digested by enzymes  Hydrolytic enzymes break down protein, carbs, and fat  Bacterial infection  Staphylococci, streptococci, and Escherichia coli o Caseous necrosis  Tuberculous pulmonary infection  Combination of coagulative and liquefactive necrosis  Cottage cheese appearance and is soft and granular o Fat necrosis  Breast, pancreas, and other abdominal organs  Action of lipases break down fat in these organs o Gangrenous necrosis  Death of tissue from severe hypoxic injury commonly from arteriosclerosis or blockage of major arteries, esp. those in legs  Dry gangrene dries and shrinks skin and color turns to dark brown or black  Wet gangrene develops when WBCs invade the site, usually internal organs causing site to become cold, swollen, and back with foul odor  Gas gangrene­ refers to special type of gangrene caused by infection of injured tissue by the bacteria clostridium  Death is caused by shock Apoptosis (programmed cell death) vs. necrosis Aging  Cellular aging o Atrophy, decreased function, and loss of cells  Tissue and systemic aging o Progressive stiffness and rigidity o Sarcopenia—loss of muscle tissue R/T aging  Frailty o Mobility, balance, muscle strength, motor activity, cognition, nutrition, endurance, falls, fractures, and bone density Somatic Death  Algor mortis—post mortem reduction of body temperature; takes about 24 hours until the body temperature equals that of the environment  Livor mortis—gravity causes blood to settle in the most dependent or lowest tissues which develop a purplish discoloration  Rigor mortis—occurs over 6­ 14 hours; muscle stiffening with smaller muscles being affected first  Putrefaction usually occurs between 24­48 hours after death as rigor mortis gradually diminishes  Body becomes flaccid in 36­62 hours