2 obj331 cellinjury
Upcoming SlideShare
Loading in...5
×

Like this? Share it with your network

Share
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
1,277
On Slideshare
1,277
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
19
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. Cell Injury and Death-viv 1. Define atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia. a. Atrophy-A decrease or shrinkage in cellular size. Most common in skeletal muscle, the heart, secondary sex organs, and the brain. Can be classified as physiological or pathological. Physiological occurs with early development (Ie. Thymus shrinkage in childhood). Pathological occurs as a result of decreases in workload , use, pressure, blood supply, nutrition, and hormonal &development nervous stimulation. b. Hypertrophy-An increase in cellular size of cells and consequently in the size of the affected organ. Cells of the heart and kidneys are responsive to enlargement. c. Hyperplasia-is an increase in the number of cells from an increase in cellular division. Two types of normal, or physiological hyperplasia are: Compensatory hyperplasia and hormonal hyperplasia. i. Compensatory hyperplasia enables certain organs to regenerate. (ie. Liver) ii. Hormonal hyperplasia occurs chiefly in estrogen dependent organs, such as the uterus and breast.(Ie. After ovulation-thickening of endometrium) iii. Pathological hyperplasia is the abnormal proliferation of normal cells and can occur as a response to excessive hormonal stimulation or the effect of growth factors on target cells. d. Dysplasia-Abnormal changes in size, shape, and organization of mature cells. e. Metaplasia- is the reversible replacement of one mature cell by another, sometimes less differentiated, cell type. 2. Identify the adaptive advantage of atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia. a. Atrophy- If a particular type of cell function in an organ or a gland is not utilized (decreased workload) or if there is an insufficient amount of physiological components (diminished blood supply, inadequate nutrition..) to maintain normal cell function then a decrease in cellular size may be beneficial. b. Hypertrophy-Meets cellular demand for increased workload. Larger cellular size contributes to increased workload. (hormone induced during pregnancy) (heart cells adapt initially to hypertension by increasing size) c. Hyperplasia-This adaptive mechanism allows certain tissues to regenerate new daughter cells due to cellular injury or physiological needs (ie hormone stimulated uterus enlargement during pregnancy.) (ex. Removal of part of the liver leads to hyperplasia of the remaining liver cells) d. Dysplasia- Is not considered to be a true adaptive advantage. It is often referred to as atypical hyperplasia. Occurs w/ irritation or inflammation in uterine cervix, gallbladder, and respiratory passages. Is reversible if irritation is removed. e. Metaplasia-The replacement of one differentiated cell with another differentiated cell. Metaplasia is reversible and usually occurs in response to chronic irritation and inflammation and allows for substitution of cells that are better able to survive under circumstances in which a more fragile cell type might succumb. (ex. In smokers, bronchial epithelial lining changes from normal columnar ciliated epithelial cells to stratified squamous epithelial cells. 3. Describe common causes of atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia. Page 1 of 7
  • 2. a. Atrophy-Decreased workload, use, pressure, blood supply, nutrition, hormonal stimulation, and nervous stimulation. Aging. b. Hypertrophy-Increased accumulation of protein in the cellular components (plasma membrane, endoplasmic reticulum, mitochondria), increased functional demand or hormone stimulation. c. Hyperplasia- Injury, cell death, hormonal stimulation. d. Dysplasia-associated with neoplastic growths and occur near cancerous growths. e. Metaplasia- Commonly thought to develop from the reprogramming of existing stem cells in most epithelia. Prolonged exposure to irritant of some type. 4. List the classes of agents that cause cell injury and cell death. Classes of agents 1.Chemical agents 5.Lack of blood supply 2.Free radicals 6.Infectious agents 3.Physical and mechanical 7.Immunological factors reactions 4.Genetic factors 8.Nutritional imbalances 3 common causes 1.Hypoxic injury 2.reactive oxygen species and free radical-induced injury 3.chemical injury 5. Describe the cellular responses to hypoxic injury and the resulting physiologic changes. Overview: Ischemic injury is often caused by gradual narrowing of arteries and completeblockage by blood clot, decreased blood flow->decreased function of the mitochondria->decreased levels of ATP-> anaerobic metabolism-> decreased ATP-> failure of the NAand K pump and sodium calcium exchange-> cellular swelling and death. Specifics: Rapid decreased mitochondrial phosphorylation, which results in insufficient ATP production. Lack of ATP leads to an increase in anaerobic metabolism generated from glycogen stores. Once glycogen stores are depleted anaerobic metabolism ceases. Na+- K+ pump and Na+-Ca++ pumps begin to fail which leads to an increase in intracellular accumulations of Na+ & Ca++. As well as potassium out of the cell. Na+ and H2O then enter the cell freely and swelling results. Dilation of the endoplasmic reticulum results from movement of water and ions into cell. Ribosomes detach from ER resulting in reduced protein synthesis. If oxygen is not restored vacuole formation occurs within Page 2 of 7
  • 3. cytoplasm, swelling of lysosomes, and marked swelling in mitochondria. Continued injury results in multiple enzyme systems DNA degeneration and Cell death. 6. Explain the source and role of free radicals in cell injury. Source Absorption of extreme energy sources--ultraviolet light & X-rays Endogenous, usually oxidative reactions occurring during metabolic processes Enzymatic metabolism of exogenous chemicals or drugs--CCl3 Role-Superoxide radical, hydroxyl radical, and hydrogen peroxide are extremely reactive andcan cause damage to nucleic acids, destroy polysaccharides, oxidize proteins,peroxidize unsaturated fatty acids, and kill and lyse cells.-Lipid peroxidation-destruction of saturated fatty acids in lipid membrane.(fatty acidscontain double bonds that are vulnerable to attack by free radicals.)The interactionbetween the radical and lipid produce peroxides that are capable of membrane, organelle,and cell destruction.-Alterations in proteins causing fragmentation of Polypeptide chains.-Alterations of DNA 7. Describe the cellular responses to chemical injury and the resulting morphological changes.Increased membrane permeability occurs due to chemical interaction with plasmamembrane, destruction of ER by way of lipid peroxidation, accumulation of lipidcomponents occurs in cytoplasm. Cellular swelling occurs because of alterations inselective permeability in the plasma membrane. Hypoxic injury occurs due to increasedsodium ion, water, and calcium ion in cytoplasm. ATP can no longer be generated by themitochondria and continued accumulation of calcium ions which cause interference withoxidative metabolism in mitochondria.8) Identify the pathogenesis and clinical significance of chemical injury caused bylead, carbon monoxide, and alcohol. (McCance and Huether Pages 55-59)Lead: Lead interferes with a variety of body processes and is toxic to many organs andtissues including the heart, bones, intestines, kidneys, and reproductive and nervoussystems. It interferes with the development of the nervous system and is thereforeparticularly toxic to children, causing potentially permanent learning and behaviordisorders. Symptoms include abdominal pain, headache, anemia, irritability, and insevere cases seizures, coma, and death.The main organ systems that are affected by lead arethe kidneys, nervous system, and the blood cell production tissues. Lead toxicity is dangerous inchildren and developing fetuses because they can absorb lead more easily. Lead exposure cancause neurological development issues and as a result patients can have learning disorders and Page 3 of 7
  • 4. attention problems. People can be exposed to lead in a variety of ways: through lead-based paint,dust and dirt containing lead, hair dyes, lead pipes for water transport, certain pottery glazes, etc.Lead symptoms increase when the individual does not have enough iron, calcium, zinc andvitamin D. Lead causes intracellular calcium to increase thereby causing cell disruptions, such asinterference with neurotransmitters. It causes damage to blood cell production processes byinhibiting enzymes that are needed for hemoglobin synthesis. The clinical manifestations oflead poisoning are: anemia, convulsions, delirium, wrist, finger and foot paralysis, nausea, loss ofappetite, loss of weight, abdominal cramping, glycosuria, aminoaciduria, and hyperphosphaturia.Carbon Monoxide: Carbon monoxide causes hypoxic injury to cells, due to its greater affinitywith hemoglobin than oxygen. It binds with hemoglobin very quickly, thereby preventing oxygenfrom binding. Unsafe CO levels are often caused by motor vehicles, malfunctioning furnaces,cigarettes and cigars. People that work as coal miners and fire fighters also have an increased riskof CO poisoning. Pregnant women should be especially concerned about CO poisoning due tothe fetus’ ability to have 10-15% higher carboxyhemoglobin levels than the mother. Clinicalmanifestations of CO are: headache, giddiness, tinnitus, nausea, weakness, and vomiting.Alcohol: Alcohol causes the most amount of injury to the liver. It also causes vitamin B, thiamin,magnesium and phosphorus deficiency. Once alcohol is consumed, it is absorbed into thestomach and small intestine where it can then spread to all tissues of the body. The majority ofthe alcohol is metabolized by the liver by hepatic alcohol dehydrogenase and the microsomalethanol oxidizing system. There are genetic differences in an individual’s ability to breakdownalcohol. Research has shown that abuse of alcohol may increase the likelihood of coronaryheart disease, but 1-2 drinks per day may actually reduce an individual’s chance ofcoronary heart disease. Clinical manifestations are: increased likelihood of hypertension andpancreatitis, and regressive changes in skeletal muscle. If a fetus is exposed to alcohol, fetalalcohol syndrome can occur and cause growth retardation, mental impairment, facial anomalies,and ocular issues. Acute alcoholism causes CNS damage, hepatic and gastric changes. Thehepatic system changes are liver enlargement, fat accumulation in the liver, prevention ofmicrotubular transport and secretion of proteins, increase intracellular water, depression of fattyacid oxidation, membrane rigidity, and necrosis of the liver. The CNS effects are motor andintellectual disorientation. Chronic alcoholism causes damage to almost every organ in the body;however, the majority of damage is shown in the liver and stomach. Often these patients havecirrhosis of the liver. Alcohol can also cause an increase in apoptosis.9) Explain the mechanism of hypothermic and hyperthermic injury. (McCance andHuether Pages 70-71)Hypothermic Injury: Ice crystals cause increased IC NA.“It causes an increase in intracellularcalcium, by slowing down the sodium/potassium pump” which causes sodium to stay in the cell(cell swelling). Hypothermia initially causes blood vessels to constrict and cause paralysis ofvasomotor control, but then vasodilation occurs followed by increased membrane permeability.This increased membrane permeability allows for swelling of the cell. Hypothermia also causesdamage to liver cells by formation of ROS. Extreme cold temperatures also cause myelin sheathdamage, which can cause motor and sensory problems. Thrombosis can also occur, which cancause gangrene.Hyperthermic Injury: The type of injury that occurs depends on the nature, intensity, and theamount of injury. Hyperthermic injury is broken down into 3 categories: Heat Cramps: Voluntary muscles become cramped. Cause: Salt and water loss due to vigorous exercise. Heat Exhaustion: Extreme salt and water loss. Hypotension occurs and the person becomes weak, nauseated, and can collapse. Page 4 of 7
  • 5. Heat stroke: The core body temperature rises to extreme levels. The individual may experience peripheral vasodialation and decreased circulating blood volume. People who are new to the military, senior citizens, athletes, or have cardiovascular problems are susceptible to this type of injury.Burns cause fluid and plasma protein loss at the location of the burn. Burn blisters are caused bydilation of blood vessels and an increase in the permeability of the membrane, which causesprotein loss. When the membrane permeability increases, cell swelling occurs. Heat also causesan increase in cellular metabolism and coagulation of blood vessels.10) Identify the common local manifestations of cell injury and why these changesoccur. (McCance and Huether Pages 73-78)Abnormal accumulations of substances in the cell cause injury: *Water- Manifestations: cellular swelling and organ appears pale. Cause: Extracellular water is drawn into the cell due to hypoxia and failure of metabolism or ATP production. Water moves into the cell because the sodium/ potassium pump no longer works which causes sodium retention in the cell, the osmotic pressure rises and water enters the cell. *Lipids and Carbohydrates- accumulation of lipids and carbohydrates in the spleen, liver and central nervous system. -Carbohydrates- Manifestations: clouding of the cornea, joint stiffness and mental retardation due to a disease called mucopolysaccharidoses. -Lipids-Manifestations: fatty liver caused by several factors from starvation to alcohol abuse. * - Glycogen-Manifestation: excessive vacuolation of the cytoplasm. Cause: Diabetes mellitis -*Proteins- Manifestations: excessive excretion of protein in the urine. Cause: A buildup of protein in the epithelial cells of the renal convoluted tubule. There can also be an abnormal level of protein found in B lymphocytes (Russell Bodies). *Pigments- Manifestations: freckles and mole coloration. Cause: melanin is gained from dying epithelial cells or melanocytes. *Hemoproteins- Hemosiderin: Manifestations: Hemosiderosis. Accumulation of hemosiderin in the areas of bruising and hemorrhage, and in the lungs and spleen after a heart failure. The color changes in bruising show the change of hemoglobin into hemosiderin. Cause: excessive storage of iron from the bloodstream. Billirubin- Manifestations: jaundice. Cause: excessive billirubin storage due to “destruction of red blood cells, diseases that affect the metabolism or excretion of billirubin, certain drugs, and/or diseases that block the common bile duct like gallstones.” Billirubin can cause a “loss of cellular proteins and uncoupling of oxidative phosphorylation.” * Calcium- accumulation of calcium Page 5 of 7
  • 6. Manifestation: Dystrophic calcification: the calcification of dying tissue of tuberculosis patients, and atherosclerosis of injured heart valves. This calcification of the heart valves and arteries can cause heart murmurs and heart attacks. Cause: exact mechanism of dystrophic calcification is unknown. Manifestation: Metastatic calcification: mineral deposits of calcium in uninjured sites due to hypercalecemia. Cause: hyperthyroidism, high levels of vitamin D, Addison’s disease, etc. *Urate- Manifestations: Gout; acute arthritis; tophus; nephritis. Causes: hyperuricemia and sodium urate crystals accumulate in tissues11) Identify systemic manifestations of cell injury. (McCance and Huether Page 79;Table 2-10)Malaise, fatigue, loss of well-beinga) Fever-endogenous pyrogens released by inflammatory responseb) Increased heart rate-increase in oxidative processes due to feverc) Increase in leukocytes-A rise in WBC’s due to an infectiond) Pain-Variety of reasons (bradykinins)e) Presence of cellular enzymes in extracellular fluid- enzymes are released from cells12) Discuss the typical tissue type, the mechanism of injury, and usual morphologyfor the following types of necrosis: coagulative, liquefactive, caseous, fat,gangrenous, and apoptosis. (McCance and Huether Pages 78-82) Coagulative: Tissue type: Kidneys, heart and adrenal glands. Mechanism ofinjury: Results from hypoxia caused by severe ischemia or chemical injury. Proteindenaturation causes coagulation of albumin. The tissue looks firm and swollen. Liquefactive: Tissue type: neurons and glial cells in the brain. Mechanism ofinjury: Caused by ischemic injury or bacterial infections. Cell ingestion occurs, bybrain’s own hydrolytic enzymes. The tissue appears soft and as its name states, itliquefies. The injured tissue is separated from healthy tissue in cysts. Caseous: Tissue type: Usually seen in Tb pulmonary infections. Caused by: It isa combination of coagualtive and liquefactive. The dead cells breakdown but debris isnot digested completely by hydrolases so tissue will look soft and granular (cheese like).The injured regions are closed off by a granulomatous inflammatory wall. Fat: Tissue type: Breast, pancreas, and other abdominal structures. Caused by:Cellular dissolution caused by lipases. “Lipases break down triglycerides and releasefatty acids that combine with Ca, Na, and Mg ions to make soaps (saponification). Tissueis opaque and chalk white.” Page 6 of 7
  • 7. Gangrenous: Tissue type: usually in lower leg. Caused by: “Results from severehypoxic injury due to arteriosclerosis or blockage of major arteries” followed by abacterial invasion. Dry gangrene is caused by coagulative necrosis. Wet gangrene iscaused by neutrophils invading and causing liquefactive necrosis. Gas gangrene is causedby an infection of Clostridium. This infection produces hydrolytic enzymes and toxinswhich ruin connective tissue and the cell membrane. Apoptosis: Tissue type: many different types. Caused by: Proteases, in responseto signals, cleave important proteins in the cell thereby killing the cell quickly and neatly.The cell shrinks, is broken down and placed into pieces. It is then phagocytized byneighbor cells. It is the active process of cell death.13) Describe genetic and environmental influences on aging. (McCance andHuether Pages 83-84)Environmental: The accumulation of injuries and events. Aging may also be caused bythe accumulation of metabolic wastes and ROS which prevent the body from maintaininghomeostasis. This as a result increases the individual’s chances of infection and disease.Genetic: Some individuals believe there is programmed aging. In other words, there is alimited amount of time for each cell to be able to replicate before it dies. It is believedthat this is caused by the human genome slowing down or shutting of physiologicalprocesses such as mitosis. The somatic mutation hypothesis states that aging is caused byDNA damage, in both repair and synthesis. The catastrophic/error-prone theory of agingstates that there are errors in the “enzymes involved in transcription and translation,which causes errors in their own synthesis and therefore lead to death of the cell.” Page 7 of 7