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.
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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 complete
blockage by blood clot, decreased blood flow->decreased function of the mitochondria->
decreased levels of ATP-> anaerobic metabolism-> decreased ATP-> failure of the NA
and 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
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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 and
can 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 acids
contain double bonds that are vulnerable to attack by free radicals.)The interaction
between 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 plasma
membrane, destruction of ER by way of lipid peroxidation, accumulation of lipid
components occurs in cytoplasm. Cellular swelling occurs because of alterations in
selective permeability in the plasma membrane. Hypoxic injury occurs due to increased
sodium ion, water, and calcium ion in cytoplasm. ATP can no longer be generated by the
mitochondria and continued accumulation of calcium ions which cause interference with
oxidative metabolism in mitochondria.
8) Identify the pathogenesis and clinical significance of chemical injury caused by
lead, 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 and
tissues including the heart, bones, intestines, kidneys, and reproductive and nervous
systems. It interferes with the development of the nervous system and is therefore
particularly toxic to children, causing potentially permanent learning and behavior
disorders. Symptoms include abdominal pain, headache, anemia, irritability, and in
severe cases seizures, coma, and death.The main organ systems that are affected by lead are
the kidneys, nervous system, and the blood cell production tissues. Lead toxicity is dangerous in
children and developing fetuses because they can absorb lead more easily. Lead exposure can
cause neurological development issues and as a result patients can have learning disorders and
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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 and
vitamin D. Lead causes intracellular calcium to increase thereby causing cell disruptions, such as
interference with neurotransmitters. It causes damage to blood cell production processes by
inhibiting enzymes that are needed for hemoglobin synthesis. The clinical manifestations of
lead poisoning are: anemia, convulsions, delirium, wrist, finger and foot paralysis, nausea, loss of
appetite, loss of weight, abdominal cramping, glycosuria, aminoaciduria, and hyperphosphaturia.
Carbon Monoxide: Carbon monoxide causes hypoxic injury to cells, due to its greater affinity
with hemoglobin than oxygen. It binds with hemoglobin very quickly, thereby preventing oxygen
from 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 risk
of CO poisoning. Pregnant women should be especially concerned about CO poisoning due to
the fetus’ ability to have 10-15% higher carboxyhemoglobin levels than the mother. Clinical
manifestations 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 the
stomach and small intestine where it can then spread to all tissues of the body. The majority of
the alcohol is metabolized by the liver by hepatic alcohol dehydrogenase and the microsomal
ethanol oxidizing system. There are genetic differences in an individual’s ability to breakdown
alcohol. Research has shown that abuse of alcohol may increase the likelihood of coronary
heart disease, but 1-2 drinks per day may actually reduce an individual’s chance of
coronary heart disease. Clinical manifestations are: increased likelihood of hypertension and
pancreatitis, and regressive changes in skeletal muscle. If a fetus is exposed to alcohol, fetal
alcohol syndrome can occur and cause growth retardation, mental impairment, facial anomalies,
and ocular issues. Acute alcoholism causes CNS damage, hepatic and gastric changes. The
hepatic system changes are liver enlargement, fat accumulation in the liver, prevention of
microtubular transport and secretion of proteins, increase intracellular water, depression of fatty
acid oxidation, membrane rigidity, and necrosis of the liver. The CNS effects are motor and
intellectual 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 have
cirrhosis of the liver. Alcohol can also cause an increase in apoptosis.
9) Explain the mechanism of hypothermic and hyperthermic injury. (McCance and
Huether Pages 70-71)
Hypothermic Injury: Ice crystals cause increased IC NA.“It causes an increase in intracellular
calcium, 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 of
vasomotor control, but then vasodilation occurs followed by increased membrane permeability.
This increased membrane permeability allows for swelling of the cell. Hypothermia also causes
damage to liver cells by formation of ROS. Extreme cold temperatures also cause myelin sheath
damage, which can cause motor and sensory problems. Thrombosis can also occur, which can
cause gangrene.
Hyperthermic Injury: The type of injury that occurs depends on the nature, intensity, and the
amount 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.
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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 by
dilation of blood vessels and an increase in the permeability of the membrane, which causes
protein loss. When the membrane permeability increases, cell swelling occurs. Heat also causes
an increase in cellular metabolism and coagulation of blood vessels.
10) Identify the common local manifestations of cell injury and why these changes
occur. (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
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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 tissues
11) Identify systemic manifestations of cell injury. (McCance and Huether Page 79;
Table 2-10)
Malaise, fatigue, loss of well-being
a) Fever-endogenous pyrogens released by inflammatory response
b) Increased heart rate-increase in oxidative processes due to fever
c) Increase in leukocytes-A rise in WBC’s due to an infection
d) Pain-Variety of reasons (bradykinins)
e) Presence of cellular enzymes in extracellular fluid- enzymes are released from cells
12) Discuss the typical tissue type, the mechanism of injury, and usual morphology
for 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 of
injury: Results from hypoxia caused by severe ischemia or chemical injury. Protein
denaturation causes coagulation of albumin. The tissue looks firm and swollen.
Liquefactive: Tissue type: neurons and glial cells in the brain. Mechanism of
injury: Caused by ischemic injury or bacterial infections. Cell ingestion occurs, by
brain’s own hydrolytic enzymes. The tissue appears soft and as its name states, it
liquefies. The injured tissue is separated from healthy tissue in cysts.
Caseous: Tissue type: Usually seen in Tb pulmonary infections. Caused by: It is
a combination of coagualtive and liquefactive. The dead cells breakdown but debris is
not 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 release
fatty acids that combine with Ca, Na, and Mg ions to make soaps (saponification). Tissue
is opaque and chalk white.”
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7. Gangrenous: Tissue type: usually in lower leg. Caused by: “Results from severe
hypoxic injury due to arteriosclerosis or blockage of major arteries” followed by a
bacterial invasion. Dry gangrene is caused by coagulative necrosis. Wet gangrene is
caused by neutrophils invading and causing liquefactive necrosis. Gas gangrene is caused
by an infection of Clostridium. This infection produces hydrolytic enzymes and toxins
which ruin connective tissue and the cell membrane.
Apoptosis: Tissue type: many different types. Caused by: Proteases, in response
to 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 by
neighbor cells. It is the active process of cell death.
13) Describe genetic and environmental influences on aging. (McCance and
Huether Pages 83-84)
Environmental: The accumulation of injuries and events. Aging may also be caused by
the accumulation of metabolic wastes and ROS which prevent the body from maintaining
homeostasis. 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 a
limited amount of time for each cell to be able to replicate before it dies. It is believed
that this is caused by the human genome slowing down or shutting of physiological
processes such as mitosis. The somatic mutation hypothesis states that aging is caused by
DNA damage, in both repair and synthesis. The catastrophic/error-prone theory of aging
states 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.”
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