chapter 3 - altered cellular and tissue biology - chapter objectives
Apoptosis
"dropping off" is an important distinct type of cell death taht differs from necrosis in several ways; is an active process of cellular self-destruction called programmed cell death and is implicated in both normal and pathologic tissue changes; Cells need to die; otherwise, endless proliferation would lead to gigantic bodies; occurs in 1) severe cell injury, 2) accumulation of misfoled proteins, 3) infections, 4) obstruction in tissue ducts; When cell injury exceeds repair mechanisms, the cell triggers apoptosis
Apoptosis vs Necrosis
Necrosis is caused by exogenous injury whereby cells are swollen and have nuclear changes in ruptured cell membrane; Apoptosis is single cell death. It is genetically programmed (suicide genes) and depends on energy. Apoptotic bodies contain part of nucleus and cytoplasmic organelles, which are ultimately engulfed by macrophages or adjacent cells; Cell membrane stays intact but has 'lubbing'; happenes throughout life and is very benificial component
Asphyxial Injuries
cuased by failure of cells to receive or use oxygen; deprivation of oxygen may be partial (hypoxia) or total (anoxia); grouped into 4 gneral categories; suffication, strangulation, chemical, and drowning
Atrophy
a decrease or shrinkage in cellular size; if atrophy happens in sufficient number of an organ's cells, the entire organ shrinks; can be physiological like thymus, pathological (disease process), or disuse; is REVERSIBLE
Caseous Necrosis
occurs in LUNGS; usually results from TB PULMONARY INFECTION, especially by Myobacterium tuberculosis; Combination of COAGULATIVE AND LIQUEFACTIVE necroses; The dead cells disintegrate, bt debris is not completely digested by hydrolases; Tissues resemble clumped cheese in that they are soft and granular; A granulomatous inflammatory wall encloses areas of caseous necrosis; Tb starts to kill lung tissue (liquefactive) and macrophages come in and stop it and coagulate the tissue - why you see tubricles in lungs
Cellular Accumulations
(infiltration); intracellular accoumulation of abnormal amounts of various substances and the resultant metabolic disturbances; results not only from sublethal, sustained injury by cells but also result from normal (but inefficient) cell function; Normal cellular substances ( excess water, proteins, lipids, carbohydrates) or abnormal substance (endogenous - product of abnormalmetabolism or synthesis, exogenous - infectious agents or minerals)
Cellular Accumulations - Glycogen
seen in genetic disorders called 'glycogen storage disease' and in disorders of glucose and glycogen metabolism; results in excessive vacuolation of cytoplasm (like water); most common cuase is diabetes mellitus; when not storing glucose or glycogen correctly, breakdown in energy of cell
Cellular Accumulations - Lipids and Carbohydrates
abnormal intercellular accumulation of carbohydrates and lipids; priamarily found in spleen, liver, and CNS; can cause "fatty liver": as lipids fill cells, vacuolation pushes the nucleus and other organelles aside; liver's outward appearance is yellow and greasy; Alcohol abuse most common cause
Cellular Accumulations - Protein
mutations in protien can slow protein folding so cell is filled with unfolded proteins, which might not be in the proper format to be used; also, metabolites (used to digest some proteins) are released from lysosomes can damage cellular organells and excessive amounts of protien in cytoplsm push against cellular organells, disrupting organelle function and intracellular communication; accumulates primarily in epithelial cells of renal confoluted tubule and antibody-forming plamsam cells (B-lymphocytes)
Cellular Accumulations - Water
cellular swelling, most common degenerative change, is caused by shift of extracellular water into cells; usually occurs in spleen, liver, CNS; cisternae of ER become distended, rupture, and then unite to form large vacuoles that isolate water from cytoplasm (called vacuolation); results in oncosis (hydropic degeneration)
Cellular Adaptations
a reversible, structural, or functional response both to normal or physiologic conditions and to adverse or pathologic conditions; Atrophy, Hypertrophy, Hyperplasia, Dysplasia, Metaplasia
Cellular Injury
most diseases begin with cell injury; occurs if the cell is unable to maintain homeostatis in face o finjurious stimulie; may be reverisble or irreversible (die)
Cellular Injury Induced by Ischemia - Irreversible
membrane damage, 2a) loss of phospholipids, alterations of cytoskeleton, activtation of inflammation (complement, cytokines, and leukocytes), increase free radicals, lipid breakdown; 3a) release of enzymes (CPK, LDH) (end), 3b) increase CA influx; 2b) increase swelling of lysosomes, 3) increased release of lysosomal enzymes (hydrolases), 4) cellular digestion (autodigestion)
Cellular Injury Induced by Ischemia - Reversible
1) obstruction or cessation of blood flow; 2) Ischemia, 3a) decrease mitochondrial oxygenation, 4a) severe vaculization of mitochondria (end); 4b) decrease ATP; 5a) decrease Na+ pump, 6) increase intracellular Na, xcellular K,intracellular Ca, 7) increase H2O, 8) increase acute cellular swelling, 5b) 5+6+7 is dilation of endoplasmic reticulum, 6) detatchment of ribosomes, 7) decrease protein synthesis, 8) lipid deposition, 5b) increase glycolysis, 6) decrease glycogen, 7) increase lactate, 8) decrease pH, 9a) nuclear chromatin clumping, 9b) increase swelling of lysosomes
Celular Death
classified as necrosis and apoptosis; Necrosis characterized by rapid loss of plasma membrane structure, organelle swelling, mitochondrial dysfunction and lack of typical features of apoptosis; Apoptosis is known as regulated or programmed cell process characterized by the "dropping off' of cellular fragments called apoptotic bodies
Chemical Asphyxiants
either prevent the delivery of oxygen to the tissues or block its utilization; doesn't allow hemaglobin to attach to oxygen or doesn't allow O2 to pass alveoli; Carbon Monoxide is the most common; Cyanide acts as an asphyxiant by combining w/ferric iron atom in cytochrome oxidase, blocking the intracellular use of oxygen, has same cherry fred appearance as a carbon monoxide intoxication; Hydrogen Sulfide (sewer gas) that may have brown-tinged blood in addition to nonspecific signs of asphyxiation
Coagulative Necrosis
occurs in KIDNEYS, HEART, and ADRENAL GLANDS commonly results from hypoxia caused by severe ischemia or hypoxia caused by chemical injury; Coagulation is cause by PROTEIN DENATURATION, which causes the protein albumin to change from gelatinous, transparent state to a firm, opaque state; bonds in protein break and they unfold
Common Themes in Cell Injury and Cell Death
ATP deletion, Reactive Oxygen Species, Ca++ entry, Mitochondrial damage, Membrane damage, Protein misfolding/DNA damage - Table 3-2
Drowning
an alteration of oxygen delivery to tissues resulting from inhalation of fluid, usually water; major mechanism of injury is hypoxemia (low blood O2 levels); can have dry-lung drowning that causes laryngospasms instead of actual water
Dry Gangrene
usually result of COAGULATIVE necrosis; SKIN becomes very dry and shrinks resulting in wrinkles, and its color changes to dark brown or black;
Dysplasia
abnormal changes in the size, shape and organization of mature cells; no considered true adaptive process but is related to hyperplaia and is often called atypical hyperplasia; often encountered in epithelial tissue of the cervix and respiratory tract; can, but not always, turn to cancer; often reversible
Fat Necrosis
is cellular dissolution caused by power enzymes, called LIPASES, that occur in BREAST, PANCREAS, and, other ABDOMINAL ORGANS; Lipases break down triglycerides, releaseing free fatty acids that then combine with calcium, magnesium and sodium ions, creating SOAPS (saponification); Necrotic tissue appears opaque and chalk-white.
Gangrenous Necrosis
refers to death of tissue from SEVERE HYPOXIC INJURY, commonly occuring beause of arteriosclerosis, or blockage of major arteries, particularly those in LOWER EXTREMITIES; With hypoxia and subsequent bacterial invasion the sittues uncergo necrosis; can be DRY, WET, or GAS
Gas Gangrene
refers to a special type of gangrene cause by INFECTION of injured tissue by one of many species of Clostridium; these anaerobic bacteria produce HYDROLYTIC ENYMES and TOXINS that detroy connective tissue and cellular membranes and cause bubbles of gas to from in muscle cells; this can be fatal if enzymes lyse the membrane of RBCs, dstorying thier O2 carrying capasity; Death is caused by shock.
Hydropic Degeneration (any type of hypoxia)
very common w/any hypoxia, even as momentary as leg falling asleep; can be reversed; 1) injury, 2) ATP production decreases, 3) sodium and water move into cell, Potassium moves out of cell, 4) Osmotic pressure increases 5) more water moves into cell, 6) cisternae of endoplasmic reticulum distend, rupture, and form vacuoles, 7) extensive vacuolation, 8) hydropic degeneration
Hyperplasia
an increase in the number of cells resulting from an increased rate of cellular division; as a response to injury, occurs when ijury has been severe and prolonged enough to have caused cell death; cells still relatively uniform, almost normal looking, just more of them; hormonal and pathologic
Hypertrophy
an increase in the size of cells and consequently in size of affected organ; heart and kidneys are very prone; associated with increased accumulation of protein in the cellular components (PM, ER, mitochondrea) and NOT with an increase in cellular fluid; can be physiologic or pathologic; is REVERSIBLE
Hypoxia
lack of sufficient oxygen; the single most common cause of cellular injury; can result from reduced amount of oxygen in air, loss of hemoglobin or decreased efficacy of hemoglobin, decreased production of RBCs, diseases of repiratory or cardovascular systems, and poisoning of the oxidative enzymes w/in cell; can induce inflammation and inflamed lesions can become hypoxic; most common form is ischemia (reduced blood supply)
Ischemia
reduced blood supply; often caused by gradual narrowing of arteries (artiosclerosis) and complete blockage by blood clots (thrombosis); progressive hypoxia caused by gradual arterial obstruction is better tlerated than acute anoxia (total lack of oxygen)
Liquefactive Necrosis
commonly results from ischemic injury to neurons and glial cells in BRAIN; dead brain tissue is readily affected because brain cells are rich in digestive HYDROLITIC ENZYMES and lipids and the brain contains little connective tissue; Cells are digested by their own HYDROLASES so the tissue becomes soft, liquefies and segregates from healthy dtissue, forming cytsts; Can be caused by BACTERIAL INFECTION, especially Staphylococci, Streptococci, and Escherichia coli.
Metaplasia
reversible replacement of one mature cell type by another, sometimes less differentiated, cell type; develops from a reprogramming of stem cells that exist on most epithelia or of undifferentiated mesenchymal cells present in connective tissue; Normal process (such as uterus); uniform to each other and relatively organized; is REVERSIBLE
Necrosis
the sum of cellular changes after local cell death and the process of cellular self-digestion, knon as autodigestion (autolysis); Damage to the plasma membrane and cell structures; 6 Major Types of Necrosis are Coagulative necrosis, Liquefactive Necrosis, Caseous Necrosis, Fat Necrosis and Gangrenous Necrosis
Strangulation
caused by compression and closure of blood vessels and air passages resulting from external pressure on neck; causes cerbral hypoxia or anoxia secondary to alteration or cessation of blood flow to and from brain; hanging (inverted V on neck), ligature (horizontal mark on neck), manual strangulation (hands on neck)
Suffocation
oxygen failing to reach the blood, can result from lack of O2 in environment (entrapment in enclosed space or filling enviro w/suffocating gas), or blockage of external airways (compression of chest, choking)
Wet Gangrene
developes when NEUTROPHILS invade the site, causing LIQUEFACTIVE necrosis; usually occurs in INTERNAL ORGANS, causing site to beome cold, swollen and black; foul odor is present, and if systemic symptoms become severe, death can ensue; Thrombisis/embolism (blockage of blood), strangulated hernia (no adequate O2 or blood), valvulus (twist of intestine), intussusception (intestine falling into self)