Chapter 3: Altered Cellular And Tissue Biology

Front 1

What can altered cellular and tissue biology result from?

Back 1

(1) adaptation
(2) injury
(3) neoplasia
(4) aging
(5) death

Front 2

What does adaptation occur in response to?

Back 2

both normal, or physiologic, conditions and adverse, or pathologic, conditions

Front 3

What is injury classified as?

Back 3

(1) chemical
(2) hypoxic (lack of sufficient oxygen)
(3) free radical
(4) intentional
(5) unintentional
(6) immunologic
(7) infection
(8) inflammatory

Front 4

How is cellular death confirmed?

Back 4

by structural changes seen when cells are stained and examined under a microscope

Front 5

What does cellular aging cause?

Back 5

structural and functional changes that eventually may lead to cellular death or a decreased capacity to recover from injury.

Front 6

Why do cells adapt to their environment?

Back 6

to escape and protect themselves from injury

Front 7

What are the most significant adaptive changes in cells?

Back 7

(1) atrophy (decrease in cell size)
(2) hypertrophy (increase in cell size)
(3) hyperplasia (increase in cell number)
(4) metaplasia (reversible replacement of one mature cell type by another less mature cell type)

Front 8

Is dysplasia (deranged cellular growth) considered a true cellular adaptation?

Back 8

no, it is considered an atypical hyperplasia

Front 9

What is atrophy?

Back 9

a decrease or shrinkage in cellular size

Front 10

What happens if atrophy occurs in a sufficient number of an organ's cells?

Back 10

the entire organ shrinks and becomes atrophic

Front 11

Atrophy can affect any organ but where is it most commonly seen?

Back 11

(1) skeletal muscle
(2) the heart
(3) secondary sex organs
(4) the brain

Front 12

When does physiologic atrophy occur?

Back 12

during early development

for example, the thymus gland undergoes physiologic atrophy during childhood

Front 13

Why does pathologic atrophy occur?

Back 13

it occurs as a result of decreases in workload, pressure, use, blood supply, nutrition, hormonal stimulation, and nervous stimulation

Front 14

What is disuse atrophy?

Back 14

a type of skeletal muscle atrophy exhibited by individuals who are immobilized in bed for a prolonged time

Front 15

What does aging cause in reference to atrophy?

Back 15

causes brain cells to become atrophic and endocrine-dependent organs, such as the gonads, to shrink as hormonal stimulation decreases

Front 16

How does an atrophic muscle cell differ from a regular muscle cell?

Back 16

it has less endoplasmic reticulum and fewer mitochondria and myofilaments (part of the muscle fiber that controls contraction) than does the normal cell

Front 17

What happens in muscular atrophy caused by nerve loss?

Back 17

oxygen consumption and amino acid uptake are immediately reduced

Front 18

List the possible mechanisms of atrophy.

Back 18

(1) decreased protein synthesis
(2) increased protein catabolism
(3) or both

Front 19

What does protein catabolism involve?

Back 19

proteosomes and ubiquitin-proteosome pathway

Front 20

What are proteosomes?

Back 20

a large protein catabolic complex in the cytoplasm

Front 21

What is the ubiquitin-proteosome pathway?

Back 21

a pathway where proteins are degraded first to ubiquitin (another small protein) and then degraded in the cytoplasm

Front 22

What plays a central role in controlling protein turnover?

Back 22

protein ubiquitination and proteolysis

Front 23

What does the deregulation of the ubiquitin-proteosome pathway lead to?

Back 23

to abnormal cell growth and is associated with cancer and other diseases

Front 24

What is the ubiquitin-proteosome pathway responsible for?

Back 24

the rapid breakdown of proteins in hypercatabolic states, including cancer cachexia

Front 25

What is atrophy resulting from chronic malnutrition often accompanied by?

Back 25

more autophagic vacuoles, which are membrane-bound vesicles within the cell that contain cellular debris and hydrolytic enzymes.

Front 26

What rises rapidly during atrophy?

Back 26

the level of hydrolytic enzymes

Front 27

Why are the hydrolytic enzymes isolated in autophagic vacuoles?

Back 27

to prevent uncontrolled cellular destruction

Front 28

Autophagic vacuoles form as needed. Why?

Back 28

to protect uninjured organelles from the injured organelles and are eventually taken up and destroyed by lysosomes

Front 29

Certain contents of the autophagic vacuole may resist destruction by lysosomal enzymes and persist in membrane-bound residual bodies. Give an example of this.

Back 29

granules that contain lipofuscin, the yellow-brown age pigment.

Lipofuscin accumulates primarily in liver cells, myocardial cells, and atrophic cells

Front 30

Where does lipofuscin accumulate in the body?

Back 30

(1) liver cells
(2) myocardial cells
(3) atrophic cells

Front 31

What cells of the body are particularly prone to enlargement by hypertrophy?

Back 31

(1) cells of the heart
(2) cells of the kidney

Front 32

What is the increase in cell size associated with? What is it not associated with?

Back 32

an increased accumulation of protein in the cellular components (plasma membrane, endoplasmic reticulum, myofilaments, mitochondria) and NOT with an increase in cellular fluid

Front 33

What is hypertrophy caused by?

Back 33

specific hormone stimulation or by increased functional demand

Front 34

List the triggers for hypertrophy.

Back 34

two types of signals:
(1) mechanical signals, such as stretch
(2) trophic signals, such as growth factors, hormones, and vasoactive agents

Front 35

Give examples of normal (physiologic) hypertrophy.

Back 35

(1) increase in skeletal muscle size due to increased workload
(2) increase in growth of uterus and mammary glands in response to pregnancy

Front 36

Give a pathologic example of hypertrophy.

Back 36

pathophysiologic hypertrophy in the heart secondary to hypertension or problem valves

Front 37

What is hyperplasia?

Back 37

an increase in the number of cells resulting from an increased rate of cellular division.

Front 38

When does hyperplasia occur in response to injury?

Back 38

when the injury has been severe and prolonged enough to have caused cell death

Front 39

What do loss of epithelial cells and cells of the liver and kidney trigger?

Back 39

triggers DNA synthesis and mitotic division

Front 40

Increased cell growth is a multistep process involving production of ____________.

Back 40

growth factors

Front 41

What do growth factors do?

Back 41

stimulate the remaining cells to synthesize new cell components and, ultimately, to divide

Front 42

What often occurs along with hyperplasia?

Back 42

hypertrophy

Front 43

When do hyperplasia and hypertrophy occur together?

Back 43

both take place if the cells can synthesize DNA

Front 44

Does hypertrophy and hyperplasia occur in nondividing cells (such as myocardial fibers)?

Back 44

in nondividing cells, only hypertrophy occurs

Front 45

What are the 3 major types of hyperplasia?

Back 45

(1) compensatory hyperplasia
(2) hormonal hyperplasia
(3) pathologic hyperplasia

Front 46

Which of the 3 major types of hyperplasia are considered normal hyperplasia?

Back 46

(1) compensatory hyperplasia
(2) hormonal hyperplasia

Front 47

What is compensatory hyperplasia?

Back 47

an adaptive mechanism that enables certain organs to regenerate

Front 48

Give an example of compensatory hyperplasia.

Back 48

removal of part of the liver leads to hyperplasia of the remaining cells (hepatocytes) to compensate for the loss.

Even with removal of 70% of the liver, regeneration is complete in about 2 weeks

Front 49

What is hepatocyte growth factor (HGF)?

Back 49

an important mediator in vitro of liver regeneration

Front 50

Which cells of the body cannot regenerate?

Back 50

(1) nerve cells
(2) skeletal muscle
(3) myocardial cells
(4) lens cells of the eye

Front 51

How are additional skeletal muscle cells made if they cannot regenerate?

Back 51

by the fusion of myoblasts

Front 52

In what parts of the body can significant hyperplasia occur?

Back 52

(1) epidermal and intestinal epithelia
(2) hepatocytes
(3) bone marrow cells
(4) fibroblasts

some hyperplasia is noted in:
(1) bone
(2) cartilage
(3) smooth muscle cells

Front 53

Give an example of compensatory hyperplasia involving epidermal cells.

Back 53

callus, or thickening, of the skin as a result of hyperplasia of epidermal cells in response to a mechanical stimulus

Front 54

Where does hormonal hyperplasia occur?

Back 54

chiefly in estrogen-dependent organs, such as the uterus and breast.

Front 55

Give an example of hormonal hyperplasia.

Back 55

after ovulation, estrogen stimulates the endometrium to grow and thicken in preparation for receiving the fertilized ovum.

if pregnancy occurs, hormonal hyperplasia, as well as hypertrophy, enables the uterus to enlarge

Front 56

What is pathologic hyperplasia?

Back 56

the abnormal proliferation of normal cells, usually in response to excessive hormonal stimulation or growth factors on target cells

Front 57

What is the most common pathologic hyperplasia?

Back 57

the pathologic hyperplasia of the endometrium (caused by an imbalance between estrogen and progesterone secretion, with oversecretion of estrogen

Front 58

What does pathologic endometrial hyperplasia cause?

Back 58

excessive menstrual bleeding

Front 59

What is pathologic endometrial hyperplasia under the influence of?

Back 59

regular growth-inhibition controls

if these controls fail, hyperplastic endometrial cells can undergo malignant transformation

Front 60

What is dysplasia?

Back 60

abnormal changes in the size, shape, and organization of mature cells

Front 61

What is dysplasia often called?

Back 61

atypical hyperplasia

Front 62

Where are dysplastic changes often encountered?

Back 62

in epithelial tissue of the cervix and respiratory tract, where they are strongly associated with common neoplastic growths and often are found adjacent to cancerous cells.

Front 63

Why is dysplasia a worrisome change in cells?

Back 63

because it is most often found near cancer cells and data indicate that it appears to be involved with breast cancer development

Front 64

How is dysplasia classified?

Back 64

mild, moderate, or severe; however, because this classification scheme is somewhat subjective, it has prompted some to recommend the use of either "low grade" or "high grade" instead.

Front 65

Can dysplastic changes be reversible?

Back 65

It can often be reversible if the inciting stimulus is removed

Front 66

What is metaplasia?

Back 66

the reversible replacement of one mature cell type by another, sometimes less differentiated, cell type.

Front 67

How is metaplasia thought to develop?

Back 67

from a reprogramming of stem cells that exist on most epithelia or of undifferentiated (embryonic) mesenchymal cells present in connective tissue

Front 68

Why do these precursor cells mature along a new pathway?

Back 68

because of signals generated by cytokines and growth factors in the cell's environment

Front 69

Give an example of metaplasia.

Back 69

replacement of normal columnar ciliated epithelial cells on the bronchial (airway) lining by stratified squamous epithelial cells.

the newly formed cells do not secrete mucus or have cilia, causing loss of a vital protective mechanism

bronchial metaplasia can be reversed if the inducing stimulus,usually cigarette smoking, is removed.

with prolonged exposure to the inducing stimulus, however, dysplasia and cancerous transformation can occur

Front 70

What do most disease begin with?

Back 70

cell injury

Front 71

When does cell injury occur?

Back 71

when the cell is unable to maintain homeostasis--a normal or adaptive steady state--in the face of injurious stimuli

Front 72

List some injurious stimuli of cells.

Back 72

(1) chemical agents
(2) lack of sufficient oxygen (hypoxia)
(3) free radicals
(4) infectious agents
(5) physical and mechanical factors
(6) immunologic reactions
(7) genetic factors
(8) nutritional imbalances

Front 73

What does the extent of cellular injury depend on?

Back 73

the type, state (including level of cell differentiation and increased susceptibility to fully differentiated cells), and adaptive processes of the cell, as well as the type, severity, and duration of the injurious stimulus

Front 74

Do two people exposed to an identical stimulus incur the same extent of cell injury?

Back 74

No, thay may incur varying degrees of of cellular injury

Front 75

Why may two individuals exposed to an identical stimulus have varying degrees of cellular injury?

Back 75

because modifying factors, such as nutritional status, can profoundly influence the extent of injury

Front 76

Can the precise "point of no return" that leads to cellular death be pinpointed to occur at a specific point?

Back 76

no

Front 77

Type of progressive cell injury: Adaptation

Give the response.

Back 77

atrophy, hypertrophy, hyperplasia, metaplasia

Front 78

Type of progressive cell injury: active cell injury

Give the response.

Back 78

immediate response of "entire" cell

Front 79

Type of progressive cell injury: reversible

Give the response.

Back 79

loss of ATP, cellular swelling, detachment of ribosomes, autophagy of lysosomes

Front 80

Type of progressive cell injury: irreversible

Give the response.

Back 80

"point of no return" structurally when severe vacuolization of the mitochondria occurs and Ca2+ moves into the cell

Front 81

Type of progressive cell injury: necrosis

Give the response.

Back 81

common type of cell death with severe cell swelling and breakdown of organelles

Front 82

Type of progressive cell injury: apoptosis, or programmed cell death

Give the response.

Back 82

cellular self-destruction for elimination of unwanted cell populations

Front 83

Type of progressive cell injury: chronic cell injury (subcellular alterations)

Give the response.

Back 83

persistent stimuli response may involve only specific organelles or cytoskeleton (e.g., phagocytosis of bacteria)

Front 84

Type of progressive cell injury: accumulations or infiltrations

Give the response.

Back 84

water, pigment, lipids, glycogen, proteins

Front 85

Type of progressive cell injury: pathologic calcification

Give the response.

Back 85

dystrophic and metastatic calcification

Front 86

List the four common biochemical themes that are important for understanding cell injury and cell death regardless of the injuring agent.

Back 86

(1) ATP depletion
(2) oxygen and oxygen-derived free radicals
(3) calcium alterations
(4) defects in membrane permeability

Front 87

List the common forms of cell injury.

Back 87

(1) hypoxic injury
(2) free radicals and reactive oxygen species injury
(3) chemical injury

Front 88

What is hypoxic cellular injury?

Back 88

lack of sufficient oxygen

Front 89

What are the common causes of hypoxic injury?

Back 89

(1) decreased amount of oxygen in the air
(2) loss of hemoglobin or hemoglobin function
(3) decreased production of red blood cells
(4) diseases of the respiratory and cardiovascular systems
(5) poisoning of the oxidative enzymes (cytochromes) within cells

Front 90

What is the most common cause of hypoxia?

Back 90

ischemia (reduced blood supply)

Front 91

What is ischemic injury often caused by?

Back 91

the gradual narrowing of arteries (arteriosclerosis), and complete blockage by blood clots (thrombosis)

Front 92

Progressive hypoxia caused by gradual arterial obstruction is better tolerated than the sudden acute ___________ caused by a sudden obstruction, as with an ______________.

Back 92

(1) anoxia (total lack of oxygen)

(2) embolus (blood clot or other plug in the circulation)

Front 93

What can an acute obstruction in a coronary artery cause?

Back 93

myocardial cell death (infarction) within minutes if the blood supply is not restored

Front 94

What does the gradual onset of ischemia in the heart usually result in?

Back 94

myocardial adaptation

Front 95

What do myocardial infarction and stroke generally result from?

Back 95

atherosclerosis (a type of arteriosclerosis) and consequent ischemic injury

Front 96

Cellular responses to hypoxic injury caused by ischemia has been demonstrated in studies of the heart muscle. Discuss.

Back 96

Within 1 minute after blood supply to the myocardium is interrupted, the heart becomes pale and has difficulty contracting normally.
Within 3 to 5 minutes, the ischemic portion of the myocardium ceases to contract because of a rapid decrease in mitochondrial phosphorylation, causing insufficient ATP production. Lack of ATP leads to increased anaerobic metabolism, which generates ATP from glycogen when there is insufficient oxygen. When glycogen stores are depleted, even anaerobic metabolism ceases.

Front 97

What does a reduction in ATP levels cause?

Back 97

the plasma membrane's sodium-potassium pump and sodium-calcium exchange to fail, which leads to an intracellular accumulation of sodium and calcium and diffusion of potassium out of the cell.

Sodium and water then can enter the cell freely, and cellular swelling, as well as early dilation of the ER, results.

Dilation causes the ribosomes to detach from the rough ER, reducing protein synthesis.

With continued hypoxia, the entire cell becomes markedly swollen, with increased concentrations of sodium, water, and chloride and decreased concentrations of potassium.

Front 98

What happens if oxygen is not restored to tissues?

Back 98

vacuolation (formation of vacuoles) occurs within the cytoplasm and swelling of lysosomes and marked mitochondrial swelling result from damage to the outer membrane.

Front 99

What does continued hypoxic injury along with accumulation of calcium activate?

Back 99

mulitple enzyme systems resulting in membrane damage, cytoskeleton disruption, activation of inflammation, DNA degradation, and eventual cell death

Front 100

What is irreversible damage characterized by?

Back 100

(1) lack of ATP generation because of mitochondrial damage (by accumulation of intracellular calcium in the mitochondria)
(2) major disturbances and damage in membrane function

Front 101

Restoration of oxygen, however, can cause additional injury called ______________.

Back 101

reperfusion injury

Front 102

What does reperfusion injury result from?

Back 102

the generation of highly reactive oxygen intermediates, sometimes called oxidative stress, including hydroxyl radical (OH-), superoxide (O2-), and hydrogen peroxide (H2O2).

Front 103

What can these radicals cause?

Back 103

further membrane damage and mitochondrial calcium overload

Front 104

What cell is especially affected with reperfusion injury?

Back 104

neutrophils, including neutrophil adhesion to the endothelium

Front 105

What reverses both neutrophil adhesion and, for example, neutrophil-meidated heart injury?

Back 105

antioxidant treatment

other potential and current treatments may include blockage of inflammatory mediators and inhibition of certain cell death (for example, apoptotic) pathways

Front 106

What is oxidative stress?

Back 106

injury induced by free radicals, especially by reactive oxygen species (ROS)

Front 107

When does oxidative stress occur?

Back 107

when excess ROS overwhelms endogenous antioxidant systems

Front 108

What is a free radical?

Back 108

an electrically uncharged atom or group of atoms that has an unpaired electron.

Front 109

What makes the free radical unstable? How does it stabilize?

Back 109

the unpaired electron

to stabilize, it gives up an electron to another molecule or steals one.

Front 110

What happens to the molecule that the free radical steals an electron from?

Back 110

it becomes a free radical and is capable of injurious chemical bond formation with proteins, lipids, and carbohydrates--key molecules in membranes and nucleic acids.

Front 111

Why are free radicals highly reactive?

Back 111

because they have low chemical specificity, meaning they can react with most molecules close by

Front 112

How may free radicals be initiated within cells?

Back 112

(1) the absorption of extreme energy sources (e.g., UV light, radiation)
(2) endogenous reactions when oxygen is reduced to water created by systems involved in electron and oxygen transport (redox reactions; all biologic membranes contain redox systems important for cell defense, for example, inflammation, iron uptake, growth, and proliferation and signal transduction)
(3) enzymatic metabolism of exogenous chemicals or drugs (e.g., CCl3, a product of carbon tetrachloride [CC14])

Front 113

During normal metabolism, what organelle is the greatest source and target of ROS?

Back 113

mitochondria

Front 114

How do ROS affect mitochondria? What are they related to?

Back 114

cause mitochondria dysfunction and are related to many human diseases and aging?

Front 115

What are ROS usually reduced by?

Back 115

intracellular antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase, and catalase, as well as antioxidant molecules such as gluthathione and vitamin E (alpha-tocopherol)

Front 116

What do ROS do in pathologic conditions?

Back 116

large numbers of ROS overwhelm the balance by antioxidants

Front 117

Why is inefficiency of antioxidants more serious in mitochondria?

Back 117

mitochondria in most cells lack catalase

Front 118

What does excessive production of hydrogen peroxide and eventually hydroxyl radical in mitochondria do?

Back 118

damage lipid, proteins, and mitochondrial DNA (mDNA), which then causes cells to die of necrosis or apoptosis

Front 119

What has mitochondrial oxidative stress been implicated in?

Back 119

heart disease
alzheimer disease
Parkinson disease
prion diseases
amyotrophic lateral sclerosis (ALS)
as well as aging itself

Front 120

What are the 4 major ways that free radicals cause cellular injury?

Back 120

(1) lipid peroxidation, which is the destruction of polyunsaturated lipids (the same process by which fats become rancid) leading to membrane damage and increased permeability
(2) attacking critical proteins that affect ion pumps and transport mechanisms
(3) fragmenting DNA, causing decreased protein synthesis
(4) damaging mitochondria, causing the liberation of calcium into the cytosol

Front 121

What does chemical injury begin with?

Back 121

a biochemical interaction between a toxic substance and the cell's plasma membrane, which is ultimately damaged, leadin gto increased permeability

Front 122

List the two general mechanisms causing chemically induced membrane destruction.

Back 122

(1) direct toxicity caused by combination of a chemical with a molecular component of the cell membrane or organelles
(2) formation of reactive free radicals and lipid peroxidation

Front 123

Give an example of chemical injury.

Back 123

carbon tetrachloride injury.

CCl4, an agent formerly used in dry cleaning, is converted by an enzyme system in the smooth ER of liver cells into CCl3 (chloromethyl), a highly toxic free radical. The newly formed CCl3, rapidly destroys the ER of the liver cell by lipid peroxidation, breaking down the reticulum's lipid component. The lipid molecules accumulate within the cytoplasm, starting within cisternae of the ER. Fatty liver develops because CCl4 poisoning blocks the synthesis of lipid-acceptor proteins (apoproteins) that normally bind with triglyercides to form lipoproteins, which are then transported out of the cell. Blockage of triglyercide secretion begins 10 to 15 minutes after CCl4 exposure. Fat droplets that accumulate in the cisternae of the ER combine to form larger droplets and fill vacuolesthat, in turn, fill the entire cytoplasm. Approx. 10 to 12 hours later, the liver appears grossly enlarged and pale because of the accumulation of fat. Fatty change is reversible if the abnormality responsible for the change is removed. At this point, the cellular changes are the same as in hypoxic injury.

Front 124

What are poisons?

Back 124

highly toxic substances

Front 125

What chemicals can cause cellular injury?

Back 125

air pollutants
insecticides
herbicides
carbon monoxide
carbon tetrachloride
social drugs, such as alcohol
recreational drugs
over-the-counter drugs
prescribed drugs

Front 126

What is lead?

Back 126

a heavy metal that persists in the environment

Front 127

What is the primary chemical hazard to children?

Back 127

lead toxicity

Front 128

Compared to adults, children absorb lead more readily through the ______________.

Back 128

intestines

Front 129

What dietary deficiencies enhance the toxic effects of lead?

Back 129

iron
calcium
zinc
vitamin D

Front 130

Why is lead exposure particularly worrisome during pregnancy?

Back 130

because the fetal nervous system is especially vulnerable and can result in learning disorders, hyperactivity, and attention problems

Front 131

Why is lead based paint attractive to children?

Back 131

because it has a sweet taste

Front 132

What are the organ systems primarily affected by lead ingestion?

Back 132

(1) nervous system
(2) hematopoietic system (tissues that produce RBCs)
(3) the kidneys

Front 133

Lead affects many different biologic activities, many of which may be related to the function of ______________,

Back 133

calcium

Front 134

What do alterations in calcium play a role in?

Back 134

the interference with neurotransmitters, which may cause hyperactive behavior and proliferation of capillaries of the white matter and arteries

Front 135

What does lead inhibit?

Back 135

several enzymes involved in hemoglobin synthesis and causes anemia as a result of lysis of red blood cells (hemolysis).

Front 136

How is lead poisoning manifested clinically?

Back 136

Alterations in calcium may play a role in the interference with neurotransmitters, which may cause hyperactive behavior and proliferation of capillaries of the white matter and arteries.

Lead inhibits several enzymes involved in hemoglobin synthesis and cuases anemia as a result of lysis of red blood cells (hemolysis).

Other manifestations of brain involvement include convulsions and delirium and, with peripheral nerve involvement, wrist, finger, and sometimes foot paralysis.

Renal lesions can cause tubular dysfunction resulting in glycosuria (glucose in the urine), aminoaciduria (amino acids in the urine), and hyperphosphaturia (excess phosphate in the urine).

Gastrointestinal symptoms are less severe and include nausea, loss of appetite, weight loss, and abdominal cramping

Front 137

How are gaseous substances classified?

Back 137

according to their ability to asphyxiate (interrupt respiration) or irritate

Front 138

What do toxic asphyxiants do?

Back 138

directly interfere with cellular respiration

Front 139

What are some examples of toxic asphyxiants?

Back 139

carbon monoxide, hydrogen cyanide, and hydrogen sulfide

Front 140

What is carbon monoxide (CO)?

Back 140

an odorless, colorless, and undetectable gas unless it is mixed with a visible or odorous pollutant

Front 141

What is carbon monoxide produced by?

Back 141

the incomplete combustion of fuels, such as gasoline

Front 142

Although carbon monoxide is a chemical agent, what is the ultimate injury it produces?

Back 142

a hypoxic injury--namely, oxygen deprivation.

Front 143

How does carbon monoxide deprive the body of oxygen?

Back 143

Normally, oxygen molecules are carried to tissues bound to hemoglobin in RBCs.
Because CO's affinity for hemoglobin is 300 times greater than that of oxygen, it quickly binds with the hemoglobin, preventing oxygen molecules from doing so.

Front 144

Minute amounts of carbon monoxide can produce a significant percentage of _________________.

Back 144

carboxyhemoglobin (carbon monoxide bound with hemoglobin)

Front 145

What symptoms are related to carbon monoxide poisoning?

Back 145

headache
giddiness
tinnitus (ringing in the ears)
nausea
weakness
vomiting

Front 146

Who are most at risk for carbon monoxide poisoning?

Back 146

those who (1) breathe air polluted by gasoline engines or defective furnaces; (2) work in occupations such as coal mining, fire fighting, welding, or engine repair; and (3) smoke cigarettes, cigars, or pipes

Front 147

Why is a fetus especially at risk from the effects of carbon monoxide?

Back 147

because fetal carboxyhemoglobin levels are likely to be 10% to 15% more than maternal levels

Front 148

What is the primary choice among mood altering drugs available in the United States?

Back 148

alcohol (ethanol)

Front 149

What are the most serious consequences of alcohol abuse?

Back 149

liver and nutritional disorders

Front 150

What major nutritional deficiencies are associated with alcohol abuse?

Back 150

magnesium
vitamin B6
thiamine
phosphorus

Front 151

How is ethanol oxidized?

Back 151

through the microsomal P-450 oxidase pathway

Front 152

What do the major effects of acute alcoholism involve?

Back 152

the CNS

Front 153

How is alcohol absorbed into the body?

Back 153

After alcohol is ingested, it is absorbed, unaltered, in the stomach and intestines.

Front 154

What can slow the rate of ethanol absorption?

Back 154

fatty foods and milk

Front 155

Where is most of the alcohol in the blood metabolized?

Back 155

in the liver

Front 156

What are the pathways in which blood alcohol is metabolized in the liver?

Back 156

(1) the major pathway involves hepatic alcohol dehydrogenase (ADH), an enzyme of the cytosol that catalyzes the conversion of ethanol to acetaldehyde
(2) the microsomal ethanol oxidizing system (MEOS) depends on cytochrome P-450, an enzyme needed for cellular oxidation. Activation of the MEOS requires a high ethanol concentration and thus is thought to be important in the accelerated ethanol metabolism (i.e., tolerance) noted in persons with chronic alcoholism

Front 157

Individuals differ in their capability to metabolize alcohol. What kind of differences have been identified?

Back 157

genetic differences in metabolism of liver alcohol, including aldehyde dehydrogenases

Front 158

Why do persons with chronic alcoholism develop tolerance?

Back 158

because of production of enzymes, leading to increased rate of metabolism (e.g., P-450)

Front 159

Discuss the J- or U-shaped inverse association between alcohol and cardiovascular disease.

Back 159

Consistent epidemiologic studies show that people who daily consume light-to-moderate (NOT excessive) amounts of alcohol reduce their risk of coronary heart disease (CHD) as compared to nondrinkers.

Front 160

What are the suggested mechanisms in which alcohol offers cardioprotection?

Back 160

(1) increased levels of high-density lipoprotein cholesterol (HDL-C)
(2) prevention of clot formation
(3) reduction in platelet aggregation
(4) lowering of plasma apolipoprotein (a) levels

Front 161

What is the suggested amount of consumption of alcohol suggested for men to reduce coronary heart disease? Women?

Back 161

Men: no more than 2 drinks per day

Women: no more than 1 drink per day

Front 162

What does acute alcoholism affect?

Back 162

affects mainly the CNS but may induce reversible hepatic and gastric changes

Front 163

What are the hepatic changes initiated by? What do the hepatic changes include?

Back 163

initiated by acetaldehyde

inflammation, depositon of fat, enlargement of the liver, interruption of microtubular transport of proteins and their secretion, increase in intracellular water, depression of fatty acid oxidation in mitochondria, increased membrane rigidity, increased reactive oxygen species, and acute liver cell necrosis

Front 164

How does alcohol affect the CNS?

Back 164

it is mainly a depressant, initially affecting subcortical structures (probably the brain stem reticular formation).

Consequently, motor and intellectual activity becomes disoriented.

At higher blood levels, medullary centers become depressed, affecting respiration.

Front 165

What does chronic alcoholism cause?

Back 165

structural alterations in practically all organs and tissues in the body because most tissues contain enzymes capable of ethanol oxidation or nonoxidative metabolism

Front 166

The most significant activity of chronic alcoholism occurs in the __________ and to a lesser extent in the _______________.

Back 166

(1) liver
(2) stomach

Front 167

What alterations of chronic alcoholism occur in the liver?

Back 167

fatty liver
alcoholic hepatitis
cirrhosis

Front 168

__________ is a direct toxic effect and chronic use can lead to acute and chronic _____________.

Back 168

(1) acute gastritis

(2) pancreatitis

Front 169

Cellular damage is increased by __________ and __________________.

Back 169

(1) reactive oxygen species (ROS)

(2) oxidative stress

Front 170

What mediates liver damage by chronic alcoholism?

Back 170

activation of proinflammatory cytokines from neutrophils and lymphocytes

Front 171

What is oxidative stress associated with during chronic alcoholism?

Back 171

cell membrane phospholipid depletion, which alters fluidity and function of cell membranes as well as intercellular support.

Front 172

What disorders is chronic alcoholism related to?

Back 172

increased tendency to hypertension and regressive changes in skeletal muscle

Front 173

What immune defects has ethanol been implicated in the onset of?

Back 173

effects on the production of cytokines involved in inflammatory responses (tumor necrosis factor alpha, interleukin-1, interleukin-6)

Front 174

What can the deleterious of prenatal alcohol exposure cause?

Back 174

mental retardation and neurobehavioral disorders, as well as fetal alcohol syndrome

Front 175

What are the symptoms of fetal alcohol syndrome?

Back 175

growth retardation
facial anomalies
cognitive impairment
ocular malformations

Front 176

What is the significantly shorter lifespan of persons with chronic alcoholism related to?

Back 176

damage to the liver, stomach, brain, and heart

Front 177

What is the most common source of human exposure to mercury?

Back 177

fish consumption
dental amalgams
vaccines

Front 178

What are the most popular and dangerous social or "recreational" drugs in the world?

Back 178

methamphetamine (METH)
marijuana
cocaine
heroin

Front 179

What is a prevalent risk among adolescents?

Back 179

"Illicit use of drugs"

Front 180

Although the prevalence of cocaine use in the general population decreased in __________, morbidity and mortality related to cocaine increased sharply in the _________.

Back 180

(1) 1986

(2) 1990s

Front 181

How many deaths were there from unintentional and intentional injuries in the US in 2002?

Back 181

161,269 deaths, an injury death rate of 55.67/100,000.

Front 182

How many deaths were there from unintentional and intentional injuries in the US in 2002?

Back 182

161,269 deaths, an injury death rate of 55.67/100,000.

Front 183

Is death more common for women than men?

Back 183

no, death is more common for men than women; the overall rate for men is 81.77/100,000 versus 31.60/100,000 for women

Front 184

Which race have the highest death rate?

Back 184

blacks: 65.65/100,000, next is whites: 55.01/100,000, and then other racial groups combined: 35.58/100,000

Front 185

What is the number one cause of death for people between the ages of 1 and 34?

Back 185

unintentional injury

Front 186

What is the 3rd leading cause of death for people between the ages of 1 and 34?

Back 186

intentional injury (suicide, homicide)

Front 187

How many deaths occur in hospitals each year according to the 1999 report by the Institute of Medicine?

Back 187

between 44,000 and 98,000 unncecessary deaths per year as a result of errors by medical professionals

Front 188

What are blunt force injuries caused by?

Back 188

the application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues

Front 189

What are the most common type of injuries seen in most health care settings?

Back 189

blunt force injuries

Front 190

Blunt force injury may be caused by __________, __________, or a combination of both.

Back 190

(1) blows (where a moving object strikes the body)
(2) impacts (where the moving body strikes a fixed object)

Front 191

What are the most common causes of blunt force injuries?

Back 191

vehicle accidents and falls, accounting for 45,579 and 17,116 deaths, respectively, in 2002

Front 192

What is a contusion?

Back 192

bleeding into the skin or underlying tissues as a consequence of a blow that squeezes or crushes the soft tissues and ruptures blood vessels without breaking the skin

(bruise)

Front 193

How long does it take for a contusion (bruise) to show up?

Back 193

it may take several hours after injury before any change in skin color is seen

Front 194

Describe the color changes a bruise (contusion) goes through.

Back 194

Initially it will be red-purple, eventually becoming blue-black, and then gradually changing to yellow-brown or green before fully disappearing

Front 195

What do the color changes of bruises reflect?

Back 195

the progression of tissue damage and healing that develops in the area of underlying injury.

Front 196

What does the length of time it takes for a bruise to resolve depend on?

Back 196

factors such as the extent and location of the injury and the degree of vascularization in the area.

small contusions may resolve in a matter of days, whereas larger ones can take weeks to completely heal

Front 197

Why may blood in deeper structures of the body be seen as bruises elsewhere?

Back 197

because blood in deeper structures may dissect along fascial planes

example, bruising of the thigh in a hip or pelvis fracture or "black eyes" in obital plate fractures

Front 198

What is a hematoma?

Back 198

a collection of blood in soft tissues or an enclosed space

Front 199

What is a subdural hematoma?

Back 199

a collection of blood between the inner surface of the dura mater and the surface of the brain, resulting in the shearing of small veins that bridge the subdural space.

Front 200

What can cause subdural hematomas?

Back 200

blows, falls, or sudden accleration/deceleration of the head, as occurs in shaken baby syndrome

Front 201

What is an epidural hematoma?

Back 201

a collection of blood between the inner surface of the skull and the dura.

Front 202

What is an epidural hematoma caused by?

Back 202

a torn artery and is almost always associated with a skull fracture

Front 203

What do contusions of the brain result from?

Back 203

(1) a blow or (2) a fall or impact

Front 204

Describe how blows cause contusions on the brain.

Back 204

in blows, when a moving object strikes the stationary head, a cerebral contusion grouped in the portions of the brain underlying the area of scalp and skull injury is known as a coup pattern of injury

Front 205

What is a coup pattern of injury?

Back 205

a cerebral contusion grouped in the portions of the brain underlying the area of scalp and skull injury

occurs when a moving object strikes the stationary head, as in blows to the head

Front 206

Describe how falls cause contusions on the brain.

Back 206

in falls, or impacts, when the moving head strikes a fixed object, a cerebral contusion seen in the area of the brain opposite the external injury is known as a contrecoup pattern of injury.

Front 207

What is a contrecoup pattern of injury?

Back 207

a cerebral contusion seen in the area of the brain opposite the external injury

results when the moving head strikes a stationary object during a fall or impact

Front 208

How does a contrecoup injury result?

Back 208

when the head accelerates and the brain lags behind and presses into the areas of the skull directly opposite the direction of motion. When the head suddenly stops, the areas of the brain pressing into the skull are injured.

Example: a person who falls directly backward, striking the occiput (back of the head), will have cerebral contusions of the frontal and termporal tips

Front 209

What does an abrasion (scrape) result from?

Back 209

the removal of the superficial layers of the skin that was caused by friction between the skin and the injuring object.

Front 210

In cases where force is applied in a transgenital, nonperpendicular direction to the skin surface, ____________ may be heaped up at the trailing or downstream edge of the abrasion.

Back 210

tags of tissue

Front 211

Describe the appearance of an abrasion.

Back 211

It will have a pale, moist, yellow-brown appearance at first. The color darkens to brown or even black as the injury dries. The injury may ooze fluid for 1 or 2 days until it is completely covered by a crust, or scab, which eventually flakes off of the underlying regenerated skin

Front 212

Abrasions and contusions may have a patterned appearance that mirrors the shape and features of an injuring object. Why is this important?

Back 212

patterning of injuries can be of crucial importance in cases of automobile accidents, assaults, or homicides; they document the connection between the victim's injuries and a suspect vehicle or weapon.

Bite marks (usually a combination of abrasion and contusion) are another example of a patterned injury that can demonstrate a link between as assailant and a victim

Front 213

What is a laceration?

Back 213

a tear or rip resulting when the tensile strength of the skin or tissue is exceeded.

Front 214

How is a laceration different from an incision?

Back 214

a laceration is much more jagged and irregular, and the edges are abraded.

an incision is where the tissue is cleanly divided by a sharp edge

Front 215

What do the depths of a laceration look like?

Back 215

irregular, and there are often tissue "bridges" of small vessels or nerves that have been stretched but not broken, crossing from one side of the wound to the other

Front 216

In a laceration, what will happen to the tissue if the injuring force is applied perpendicularly to the skin?

Back 216

there will be crushing of the surrounding tissue with associated abrasion and contusion.

Front 217

In a laceration, what will happen to the tissue if the injuring force is applied tangenitally?

Back 217

there will also be undermining of the wound, with tissues at the trailing edge of the wound lifted away from the underlying structures creating a pocket in the direction opposite from where the blow came.

Front 218

What is an avulsion?

Back 218

an extreme example of when an injuring force is applied tangenitally to the skin, in which a wide area of tissue may be pulled away creating a larger flap.

usually, the shallower the angle of incidence of the blow, the more extensive the undermining

Front 219

What are lacerations of internal organs more common in?

Back 219

blunt force injuries

Front 220

What kind of lacerations can occur in cases of blows to the abdomen?

Back 220

lacerations of the liver, spleen, kidneys, and bowels

Front 221

What can be lacerated in sudden deceleration accidents? Why?

Back 221

the thoracic aorta

because the arch of the aorta is freely mobile, whereas the descending portion is attached to the spinal column. Rapid deceleration causes horizontal shearing with either partial or complete transection just below the take-off of the left subclavian artery.

Front 222

What can severe blows or impacts to the chest cause?

Back 222

rupturing of the heart with lacerations of the atria or ventricles

Front 223

What are fractures?

Back 223

the breakage or shattering of bones during blunt force blows or impacts

Front 224

How many deaths did cutting or piercing injuries (sharp-force injuries) account for in 2002?

Back 224

2,762, with men having a higher (1.44/100,000) than women (.49/100,000). There also are differences among races, with rates in whites at 0.73/100,000, blacks at 2.33/100,000, and other racial groups at 0.96/100,000

Front 225

What is an incised wound?

Back 225

a cut that is LONGER than it is DEEP.

Front 226

Describe the appearance of an incised wound?

Back 226

the wound may be straight or jagged, depending on the object used and how the injury occurred, with sharp, distinct edges without abrasion

may be thin and narrow or more elliptic and gaping in appearance because of varying lines of tension in the skin, location, and orientation

Front 227

What are incised wounds caused by?

Back 227

a sharp edge, which cleanly divides the tissues causing no tissue bridging or undermining

Front 228

What type of bleeding do incised wounds cause?

Back 228

tend to produce significant external bleeding with minimal internal hemorrhage

Front 229

Where are incised wounds most often seen?

Back 229

in sharp-force injury suicides

in most cases, in addition to a deep, lethal cut, there will be multiple superficial incisions grouped in the same area; these are known as hesitation marks

Front 230

What are hesitation marks?

Back 230

multiple superficial incisions grouped in the same area as the deep, lethal cut in suicides

Front 231

What is a stab wound?

Back 231

a penetrating sharp-force injury that is DEEPER than it is LONG.

Front 232

Since a sharp instrument is used to inflict a stab wound, what do the depths of the wound look like?

Back 232

clean and distinct with no underlying or associated crushing injury

t

Front 233

What do the edges look like in an injury caused by a stab wound?

Back 233

usually are clean but may be abraded if the object is inserted deeply with enough force so that a wider, blunter portion of the instrument (e.g., hilt of a knife) impacts the skin

Front 234

How can features of the blade used to inflict injury in a stab wound be determined?

Back 234

by careful examination of the stab wound

Front 235

How will a stab wound look if a single-edge blade is used?

Back 235

one margin of the wound will be sharp and the other blunt

Front 236

How will a stab wound look if a double-edge blade is used?

Back 236

both margins will have a sharp appearance

Front 237

How will a stab wound look if a serrated edge blade is used?

Back 237

often indistinguishable from those made by a smooth-edge blade

Front 238

How will a stab wound look if there was any hesitation or scraping of the skin edges by the blade?

Back 238

an interrupted pattern of abrasion may be seen but is uncommon

Front 239

What type of objects may produce penetrating puncture wounds?

Back 239

instruments or objects with sharp points but without sharp edges

Front 240

Give an example of a puncture wound.

Back 240

a wound of the foot caused by stepping on a nail

Front 241

How do injuries caused by puncture wounds look?

Back 241

have abrasion of the edges of the wound, are prone to infection, and also can be quite deep despite a sometimes innocuous external appearance

Front 242

What types of instruments produce chopping wounds?

Back 242

heavy, edged instruments (axes, hatchets, propeller blades)

Front 243

What are some characteristics of chopping wounds?

Back 243

a combination of sharp- and blunt-force characteristics

in addition to cutting, associated crushing of the wound edges and underlying tissues is usually present

Front 244

How many deaths were caused by gunfire injuries in 2002?

Back 244

30,242 deaths

of these, 17,108 were suicides, 11,829 were homicides, 762 were accidents, and 243 wer classified as undetermined

Front 245

Gunshot wounds may be either ___________ or ______________.

Back 245

(1) penetrating (bullet retained in the body)
(2) perforating (bullet exits)

Front 246

What are the most important factors determining the appearance of a gunshot injury?

Back 246

(1) whether it is an entrance or exit wound
(2) the range of fire

Front 247

What is the overall appearance of an entrance wound most affected by?

Back 247

the range of fire

Front 248

When do contact range entrance wounds occur?

Back 248

when the gun is held so that the muzzle rests on or presses into the skin surface, causing a distinctive type of wound

Front 249

What do contact range entrance wounds look like?

Back 249

in addition to the hole made by the bullet, there is searing of the edges of the wound from the flame, hot gases exiting the barrel, and soot or smoke deposited on the edges of and in the depths of the wound

Front 250

How do hard contact wounds look?

Back 250

there may be minimal soot and searing on the outside of the outside of the wound but deep penetration of smoke, burning gunpowder fragments, and hot gases into the depths of the injury

hard contact wounds of the head, where there is only a thin layer of skin and muscle overlying bone, the large amount of gas and explosive energy sent into the wound may cause severe tearing and disruption of the tissues, giving the wound a large, gaping, and jagged appearance--a phenomenon known as blow back.

in areas of the body with thicker layers of soft tissue, the blow back may not cause tearing but will forcefully drive the skin back onto the end of the barrel, producing a patterned abrasion that mirros the feature of the weapon, known as a muzzle imprint

Front 251

What are the characteristics of intermediate (distance) range entrance wounds?

Back 251

wounds surrounded by gunpowder stippling or tattooing

Front 252

What does tattooing result from?

Back 252

fragments of burning or unburned pieces of gunpowder exiting the barrel and striking the skin surface with enough force to be driven into the epidermis or superficial dermis

Front 253

When does stippling result?

Back 253

when fragments of powder strike with enough force to abrade the skin but not actually penetrate the surface

Front 254

When can stippling/tattooing be seen?

Back 254

when the muzzle-to-target range of most handguns is less than 48 inches. Beyond this distance, pieces of gunpowder disperse and slow down so much that tatooing or stippling cannot occur

Front 255

When does an indeterminate range entrance wound occur?

Back 255

when flame, soot, or gunpowder does not reach the skin surface and the only thing striking the body is the bullet.

example: if an individual is shot through multiple layers of clothing, the entrance wound may have no soot, searing, or stippling even though the actual range of fire is only a matter of inches; the wound looks the same as if the shot came from a range of 6 meters (20 feet) or more

Front 256

What are indeterminate range entrance wounds characterized by?

Back 256

a hole surrounded by a rim of abrasion

Front 257

True or False. The caliber of weapon that inflicted the wound can be determined based solely on the size of the entrance wound.

Back 257

FALSE

Front 258

What does the collar of abrasion of a gunshot wound result from?

Back 258

the fact that the bullet first causes stretching and scraping of the skin before it actually perforates.

if the bullet strikes perpendicularly to the skin, the margin of abrasion collar is concentrically distributed about the defect; if it strikes at an angle, the collar is eccentric, with the wider margin pointing in the direction from which the bullet cam from

if the bullet struck an intermediate object before hitting the skin, it can be turning and tumbling, producing an irregular abrasion collar

Front 259

True or False. Exit wounds have the same general appearance no matter what the range of fire.

Back 259

TRUE

Front 260

What can the shape of the exit wound look like?

Back 260

can vary from round to slitlike to completely irregular

Front 261

True or False. The size of the exit wound correlates with the caliber of the projectile making the wound.

Back 261

FALSE

Front 262

What are the most important factors affecting exit wounds?

Back 262

(1) the speed of the projectile
(2) the degree of deformation

Front 263

What type of wound can be produced by a smaller, highly deformed bullet exiting at high speed? What about a larger, intact, slower-moving bullet?

Back 263

a large, irregular wound, whereas a larger, more intact, slower-moving bullet may make only a small hole

Front 264

True or False. Size can be used to determine if the hole is an exit wound or entrance wound.

Back 264

FALSE

Front 265

List the general appearance characteristics of an exit wound.

Back 265

in most cases, the margins of an exit wound do NOT have an abrasion collar.

An exit wound has clean edges that often can be reapproximated to cover the defect. The exception is when something pressing against the skin surface at the exit site, such as tight clothing or the back of a chair. In that situation, the bullet pushes against the supporting surface, causing rubbing and scraping around the exit defect as it comes out; this is known as a shored exit wound

Front 266

What is a shored exit wound?

Back 266

an exit wound where the bullet pushes the skin against a supporting surface (e.g., tight clothing or the back of a chair), causing rubbing and scraping around the exit defect as it comes out

Front 267

What is one of the toughest structures for a bullet to go through?

Back 267

the skin

Front 268

What is the damage caused by a bullet the result of?

Back 268

the amount of energy transferred to the tissues impacted

Front 269

What is the formula that determines the energy of a bullet?

Back 269

KE=1/2 MV^2, where KE is kinetic energy, M is the mass, and V is the speed

Front 270

What has the greater effect on the potential for a bullet to cause damage?

Back 270

increasing the speed of the bullet rather than increasing the size of the bullet

Front 271

What does the energy transfer of a bullet to tissues cause?

Back 271

tissue destruction in a zone that can be much larger than the actual size of the bullet; the zone of destruction may be several inches in diameter with very high-powered bullets.

Front 272

True or False. When a victim has a "lethal" injury, he/she is always immediately incapacitated.

Back 272

FALSE

Front 273

What are asphyxial injuries caused by?

Back 273

a failure of cells to receive or utilize oxygen

Front 274

Deprivation of oxygen may be __________ or ___________.

Back 274

(1) partial (hypoxia)
(2) total (anoxia)

Front 275

What are the 4 general categories that asphyxial injuries are grouped into?

Back 275

(1) suffocation
(2) strangulation
(3) chemical asphyxiants
(4) drowning

Front 276

What is suffocation?

Back 276

oxygen failing to reach the blood

Front 277

What can suffocation result from?

Back 277

a lack of oxgyen in the environment (entrapment in an enclosed space or filling of the environment with a suffocating gas) OR
blockage of the airways

Front 278

Give an example of an asphyxial injury.

Back 278

child trapped in an abandoned refrigerator or a person who commits suicide by putting a plastic bag over their head

Front 279

A reduction in ambient oxygen level to ____% (normal is 21%) is immediately dangerous.

Back 279

16%

Front 280

If the level of ambient oxygen is below ____%, death can ensue within a matter of minutes.

Back 280

5%

Front 281

How are suffocation injuries diagnosed?

Back 281

depends on knowing the history of what happened because there will be no specific physical findings

Front 282

What does diagnosis and treatment in choking asphyxiation (obstruction of the airways) depend on?

Back 282

locating and removing the obstructing material

Front 283

Besides the most common causes of suffocation, what are other causes?

Back 283

injury or disease that causes swelling of the soft tissues of the airway leading to partial or complete obstruction and subsequent asphyxiation

compression of the chest or abdomen (mechanical or compressional asphyxia) preventing normal respiratory movements.

Front 284

What are the usual signs and symptoms of suffocation?

Back 284

florid facial congestion and petechia (pinpoint hemorrhages) of the eyes and face

Front 285

What is strangulation caused by?

Back 285

compression and closure of the blood vessels and air passages resulting from external pressure on the neck

Front 286

What does strangulation cause?

Back 286

cerebral hypoxia or anoxia secondary to the alteration or cessation of blood flow to the brain

Front 287

How much force is needed to close the jugular veins? Carotid arteries?

Back 287

(1) 2 kg or 4.5 lbs
(2) 5 kg or 11 lbs

Front 288

How much force is needed to crush the trachea?

Back 288

15kg or 33 lbs

Front 289

What actually causes death or injury in strangulations?

Back 289

the alteration of cerebral blood flow, NOT the lack of airflow

Front 290

How long does it take for unconsciousness to occur with complete blockage of the carotid arteries?

Back 290

10 to 15 seconds

Front 291

What are hanging strangulations?

Back 291

strangulation in which a noose is placed around the neck, and the weight of the body is used to cause constriction of the noose and compression of the neck

Front 292

True or False. In a hanging strangulation, the body needs to be completely suspended to produce severe injury or death.

Back 292

False

Front 293

What are the characteristics of hanging strangulations?

Back 293

depending on the type of ligature used, there is usually a distinct mark on the neck, an inverted V with the base of the V pointing toward the point of suspension.

Internal neck injuries are rare, and only in judicial hangings, where the body is weighted and dropped, will significant soft tissue or cervical spinal trauma be seen.

Petechiae of the eyes or face may be seen, but they are rare.

Front 294

What are the characteristics of ligature strangulations?

Back 294

marks on the neck are horizontal without the inverted V seen in hangings.

Petechiae may be more common because intermittent opening and closure of the blood vessels may occur as a result of the victim's struggles.

internal injuries of the neck are rare

Front 295

Why is petechiae more common in ligature strangulations?

Back 295

because intermittent opening and closure of the blood vessels may occur as a result of the victim's struggles.

Front 296

What type of neck injuries are found in manual strangulation caused either by the assailant or by the victim clawing at his or her own neck in an attempt to remove the assailant's hands?

Back 296

variable amounts of external trauma on the neck with contusions and abrasions

Front 297

Do manual strangulations cause internal damage?

Back 297

yes, it can be quite severe, with bruising of deep structures and even fractures of the hyoid bone and tracheal and cricoid cartilages.

Petechiae are common.

Front 298

How do chemical asphyxiants work?

Back 298

by either preventing the delivery of oxygen to the tissues OR block its utilization

Front 299

What is the most common chemical asphyxiant?

Back 299

carbon monoxide

Front 300

How does cyanide act as an asphyxiant?

Back 300

by combining with the ferric iron atom in cytochrome oxidase, thereby blocking the intracellular utilization of oxygen

Front 301

What are the signs/symptoms of cyanide poisoning?

Back 301

cherry-red appearance like carbon monoxide intoxication because cyanide blocks the utilization of circulating oxyhemoglobin

Front 302

Does cyanide produce a characteristic odor?

Back 302

yes, an odor of bitter almonds may be detected but the ability to smell cyanide is a genetic trait that is absent in a significant portion of the population, so it may not be smelled

Front 303

What is hydrogen sulfide (sewer gas)?

Back 303

a chemical asphyxiant in which victims of hydrogen cyanide poisoning may have brown-tinged blood in addition to the nonspecific signs of asphyxiation

Front 304

What is drowning?

Back 304

an alteration of oxygen delivery to tissues resulting from the breathing in of fluid, usually water

Front 305

How many drowning deaths were there in the US in 2002?

Back 305

4,146 deaths

Front 306

What is the major mechanism of injury in drowning?

Back 306

hypoxemia (low blood oxygen levels)

Front 307

What is the most important pathologic abnormality in drownings?

Back 307

airway obstruction

Front 308

In as many as ____% of drownings little or no water enters the lungs because of _________________. This phenomenon is called ___________________.

Back 308

(1) 15%
(2) vagal nerve-mediated laryngospasms
(3) dry-lung drowning

Front 309

No matter what mechanism is involved, ______________ will lead to unconsciousness in minutes.

Back 309

cerebral hypoxia

Front 310

What determines if unconsciousness caused by cerebral hypoxia progresses to death?

Back 310

depends on a number of factors, including age and the health of the individual

one of the most important factors is the temperature of the water. Irreversible injury will result more rapidly in warm water than in cold water. Submersion times up to 1 hour with subsequent survival have been reported in children who wer submerged in very cold water.

Front 311

True or False. Complete submission is necessary for a person to drown.

Back 311

False. An incapacitated or helpless individual (epileptic, alocholic, infant) may drown in water that is only a few inches deep.

Front 312

True or False. No specific or diagnostic findings prove that a person recovered from water is actually a drowning victim.

Back 312

True. In cases where water has entered the lung, there may be large amounts of foam coming out of the nose and mouth, although this also can be seen in certain types of drug overdoses. A body recovered from water with signs of prolonged immersion could just as easily be a victim of some other type of injury that has been put in the water to obscure the actual cause of death.

Front 313

What does the pathogenicity (virulence) of microorganisms depend on?

Back 313

their ability to survive and proliferate in the human body, where they injure cells and tissues

Front 314

What does the disease-causing ability of a microorganism depend on?

Back 314

its ability to (1) invade and destroy cells, (2) produce toxins, and (3) produce damaging hypersensitivity reactions

Front 315

What are injured by direct contact with cellular and chemical components of the immune and inflammatory responses, such as phagocytic cells (lymphocytes, macrophages) and substances such as histamine, antibodies, lymphokines, complement, and proteases?

Back 315

cellular membranes

Front 316

What is responsible for many of the membrane alterations that occur during immunologic injury?

Back 316

complement

Front 317

What are membrane alterations associated with?

Back 317

a rapid leakage of potassium out of the cell and rapid influx of water

Front 318

How do antibodies interfere with membrane function?

Back 318

by binding to and occupying receptor molecules on the plasma membrane

Front 319

How do antibodies interfere with cellular communication?

Back 319

by blocking or destroying cellular junctions

Front 320

List some mechanisms of cellular injury.

Back 320

(1) genetic factors
(2) nutritional imbalances
(3) physical agents

Front 321

What are some physical agents that can cause cellular injury?

Back 321

(1) temperature extremes
(2) atmospheric pressure
(3) ionizing radiation
(4) illumination
(5) mechanical stresses
(6) noise

Front 322

When do cellular accumulations occur?

Back 322

(also called infiltrations)

occur not only when injury is sublethal and sustained in injured cells but also in normal cells

Front 323

What do common cellular accumulations consist of?

Back 323

substances that are normally present, such as fluids and electrolytes, triglycerides (lipids), glycogen, calcium, uric acid, proteins, melanin, and bilirubin

Front 324

When do abnormal accumulations of substances occur in the cytoplasm (often in the lysosomes)?

Back 324

if (1) the normal, endogenous substance is produced in excess or at an increased rate; (2) an endogenous substance (normal or abnormal) is not effectively catabolized, usually because of lack of a vital lysosomal enzyme; or (3) harmful exogenous materials, such as heavy metals, mineral dusts, or microorganisms, accumulate because of inhalation, ingestion, or infection

Front 325

In all storage diseases, what do cells attempt to do? What happens as a result of this?

Back 325

(1) cells attempt to digest, or catabolize, the "stored" substances

(2) as a result, excessive amounts of metabolites (products of catabolism) accumulate in the cells and are expelled into the extracellular matrix, where they are taken up by phagocytic cells called macrophages

as more and more macrophages and other phagocytes migrate to tissues that are producing excessive metabolites, the afftected tissues begin to swell. This is the mechanism that causes enlargement of the liver (hepatomegaly) or the spleen (splenomegaly) as a clinical manifestation of many storage diseases

Front 326

List two clinical manifestations of storage diseases.

Back 326

(1) hepatomegaly (enlargement of the liver)

(2) splenomegaly
(enlargement of the liver)

Front 327

What is the most common degernative change in cells?

Back 327

cellular swelling

Front 328

What is cellular swelling caused by?

Back 328

the shift of extracellular water into the cells.

Front 329

In hypoxic injury, what is the movement of fluid and ions into the cell associated with?

Back 329

acute failure of metabolism and loss of ATP production

Front 330

How does hypoxic injury cause acute failure of metabolism and loss of ATP production?

Back 330

Normally, the pump that transports sodium ions out of the cell is maintained by the presence of ATP and ATPase, the active-transport enzyme.

In metabolic failure caused by hypoxia, reduced ATP and ATPase permit sodium to accumulate in the cell while potassium diffuses outward.

The inreased intracellular sodium increases osmotic pressure, drawing more water into the cell.
The cisternae of the ER become distended, rupture, and coalesce to form large vacuoles that isolate the water from the cytoplasm, a process called vacuolation.

Front 331

What does progressive vacuolation result in?

Back 331

in oncosis or vacuolar degeneration or swelling (degeneration by water).

if cellular swelling affects all the cells in an organ, the organ increases in weight and becomes distended and pale.

Front 332

What is oncosis?

Back 332

a form of cell death where the mechanism is failure of the sodium/potassium pumps of the plasma membrane.

Front 333

What is oncosis caused by?

Back 333

by ischemia and possibly by toxic agents that interfere with ATP generation

Front 334

How long does it take for oncosis to evolve into cellular death?

Back 334

about 24 hours

Front 335

What is cell death usually accompanied by?

Back 335

nuclear dissolution

Front 336

True or False. Cellular swelling is reversible.

Back 336

True

Front 337

What is the early manifestation of almost all types of cellular injury?

Back 337

cellular swelling

Front 338

What is cellular swelling associated with?

Back 338

high fever
hypokalemia (abnormally low concentration of potassium in the blood)
certain infections

Front 339

What do certain metabolic disorders result from?

Back 339

the accumulation of carbohydrates and lipids

Front 340

Where are accumulations of carbohydrates and lipids primarily found in?

Back 340

spleen, liver, and CNS

Front 341

What does the accumulation of carbohydrates and lipids in the CNS cause?

Back 341

neurologic dysfunction and severe mental retardation

Front 342

In what diseases is lipid accumulation involved?

Back 342

Tay-Sachs disease
Niemann-Pick disease
Gaucher disease

Front 343

In what diseases are carbohydrates normally in excess?

Back 343

diseases known as mucopolysaccharidoses

Front 344

What are mucopolysaccharidoses?

Back 344

progressive disorders that usually involve multiple organs, including liver, spleen, heart, and blood vessels

Front 345

Where are accumulated mucopolysaccharides found in?

Back 345

reticuloendothelial cells, endothelial cells, intimal smooth muscle cells, and fibroblasts throughout the body

Front 346

What do carbohydrate accumulations cause?

Back 346

clouding of the cornea
joint stiffness
mental retardation

Front 347

Although lipids sometimes accumulate in the heart and kidney cells, what is the most common site of intracellular llipid accumulation, or fatty change?

Back 347

in liver cells

Front 348

Hepatic metabolism and secretion of lipids are crucial to proper body function. What do imbalances and deficiencies in these processes lead to?

Back 348

major pathologic changes: lipid accumulation in liver cells causes fatty liver, or fatty change.

As lipids fill the cells, vacuolation pushes the nucleus and other organelles aside. Grossly, the liver looks yellowish and greasy.

Front 349

What does a fatty liver look like?

Back 349

yellowish and greasy

Front 350

When does lipid accumulation in liver cells occur?

Back 350

after cellular injury sets one or more of the following mechanisms in motion:
(1) increased movement of free fatty acids into the liver (starvation, for example, increases breakdown of triglycerides in adipose tissue, releasing fatty acids that subsequently enter liver cells)
(2) failure of the metabolic process that converts fatty acids to phospholipids, resulting in the preferential conversion of fatty acids to triglycerides
(3) increased sythesis of triglycerides from fatty acids (increases in an enzyme, alpha-glycerophosphatase, can accelerate triglyceride synthesis)
(4) decreased synthesis of apoproteins (lipid-acceptor proteins)
(5) failure of lipids to bind with apoproteins and form lipoproteins
(6) failure of mechanisms that transport lipoproteins out of the cell

Front 351

What diseases and disorders are intracellular accumulations of glycogen seen?

Back 351

genetic disorders called glycogen storage diseases and in disorders of glucose and glycogen metabolism.

Front 352

What does glycogen accumulation result in?

Back 352

excessive vacuolation of the cytoplasm

Front 353

What is the most common cause of glucose accumulation?

Back 353

the disorder of glucose metabolism, diabetes mellitus

Front 354

What is the function of protein in the cell?

Back 354

cellular structure

Front 355

What consitutes most of the cell's dry weight?

Back 355

proteins

Front 356

Where are proteins synthesized?

Back 356

on ribosomes in the cytoplasm

Front 357

Which essential amino acids are proteins synthesized from?

Back 357

lysine
threonine
leucine
isoleucine
methionine
tryptophan
valine
phenylalanine
histidine

Front 358

What are the two ways in which protein accumulation damages a cell?

Back 358

(1) metabolites produced when the cell attempts to digest some proteins, are enzymes that, when released from lysosomes, can damage cellular organelles
(2) excessive amounts of protein in the cytoplasm push against cellular organelles, disrupting organelle function and intracellular communication

Front 359

Where does excess protein primarily accumulate?

Back 359

in the epithelial cells of the renal convoluted tubule and in the antibody-forming plasma cells (B lymphocytes) of the immune system

Front 360

What types of disorders causes excessive excretion of protein molecules into the urine (proteinuria)?

Back 360

several types of renal disorders

Front 361

What does the presence of a significant amount of protein in the urine indicate?

Back 361

cellular injury and altered cellular function

Front 362

What does protein accumulation in the cytoplasm of renal tubular cells signify?

Back 362

signify a pathologic process but does not cause direct cellular dysfunction

Front 363

When can accumulations of protein in B lymphocytes occur?

Back 363

during active synthesis of antibodies during the immune response

Front 364

What are excessive aggregates of protein called in B lymphocytes?

Back 364

Russell bodies

Front 365

What disease has Russell bodies be identified in?

Back 365

multiple myeloma (plasma cell tumor)

Front 366

Pigment accumulation may be _______ or _________, _________ or __________.

Back 366

(1) normal
(2) abnormal
(3) endogenous
(4) exogenous

Front 367

Give an example of where endogenous pigments are derived.

Back 367

amino acids (e.g., tyrosine, tryptophan)

Front 368

Give an example of an endogenous pigment.

Back 368

melanin
blood proteins (poryphyrins, hemoglobin, and hemosiderin)

Front 369

Give an example of a lipid-rich pigment.

Back 369

lipofuscin--aging pigment--gives a yellow-brown color to cells undergoing slow, regressive, and often atrophic changes

Front 370

Give examples of exogenous pigments.

Back 370

mineral dusts containing silica and iron particles, lead, silver salts, and dyes for tattoos

Front 371

Where does melanin accumulate?

Back 371

in epithelial cells (keratinocytes) of the skin and retina

Front 372

Why is melanin an important pigment?

Back 372

because it protects the skin against long exposure to sunlight and is considered an essential factor in the prevention of skin cancer

Front 373

What stimulates the synthesis of melanin? What is the function of melanin?

Back 373

UV light stimulates the synthesis of melanin, which probably absorbs UV rays during subsequent exposure.

Melanin may also protect the skin by trapping the injurious free radicals produced by the action of UV light on the skin.

Front 374

What is melanin?

Back 374

a brown-black pigment derived from the amino acid tyrosine

Front 375

What is melanin synthesized by? Where is it stored?

Back 375

epidermal cells called melanocytes and is stored in membrane-bound cytoplasmic vesicles called melanosomes

Front 376

Where does melanin accumulate? How do these cells acquire the melanin?

Back 376

in melanophores (melanin-containing pigment cells), macrophages, or other phagocytic cells in the dermis

Presumably, these cells acquire the malanin from nearby melanocytes or from pigment that has been extruded from dying epidermal cells.

Front 377

What causes freckles?

Back 377

cells acquire melanin from nearby melanocytes or from pigment that has been extruded from dying epidermal cells

Front 378

Melanin also occurs in the benign form of pigmented moles. What are these moles called?

Back 378

nevi

Front 379

What is malignant melanoma?

Back 379

a cancerous skin tumor than contains melanin

Front 380

In what disorder does a decrease in melanin production occur?

Back 380

the inherited disorder of melanin metabolism called albinism

Front 381

Besides melanin metabolism, what other metabolism is albinism also related to?

Back 381

phenylalainin metabolism

Front 382

In classic types of albinism what is the person unable to do?

Back 382

unable to convert tyrosin to DOPA (3,4-dihydroxyphenylalanine), an intermediate in melanin biosynthesis.

Front 383

True or False. In albinism, melanin-producing cells are present in NORMAL numbers.

Back 383

True. They are just not able to make melanin

Front 384

What proteins are among the most essential of the normal endogenous pigments?

Back 384

hemoproteins

Front 385

List the hemoproteins.

Back 385

hemoglobin
the oxidative enzymes, the cytochromes

Front 386

What knowledge is necessary in order to understand the disorders of the hemoproteins?

Back 386

knowledge of iron uptake, metabolism, excretion, and storage

Front 387

What is hemoprotein accumulation in cells caused by?

Back 387

excessive storage of iron, which is transferred to the cells from the bloodstream

Front 388

What are the 3 primary sources by which iron enters the blood?

Back 388

(1) tissue stores
(2) the intestinal mucosa
(3) macrophages that remove and destroy dead or defective red blood cells

Front 389

Besides the 3 primary sources by which iron enters the blood, what does the amount of iron in blood plasma depend on?

Back 389

the metabolism of the major iron-transport protein, transferrin

Front 390

What are the 2 forms in which iron is stored in tissue cells?

Back 390

(1) as ferritin
(2) as hemosiderin, when increased levels of iron are present

Front 391

What is hemosiderin?

Back 391

a yellow-brown pigment derived from hemoglobin

Front 392

In pathologic states, where does excesses of iron cause hemosiderin to accumulate in cells?

Back 392

often in areas of bruising or hemorrhage and in the lungs and spleen after congestion caused by heart failure

Front 393

What transformation is reflected in the color changes noted with bruising?

Back 393

with local hemorrhage, the skin first appears red-blue and then lysis of the escaped red blood cells occurs, causing the hemoglobin to the transformed to hemosiderin

Front 394

What is hemosiderosis?

Back 394

a condition in which excess iron is stored as hemosiderin in the cells of many organs and tissues

Front 395

What type of individuals is hemosiderosis common?

Back 395

in individuals who have received repeated blood transfusions or prolonged parenteral administration of iron

Front 396

What is hemosiderosis associated with?

Back 396

increased absorption of dietary iron, conditions in which iron storage and transport is impaired, and hemolytic anemia

Front 397

Excessive ingestion of what substance can cause hemosiderosis?

Back 397

alcohol (wine)

Front 398

How is excessive absorption of dietary iron normally prevented?

Back 398

by an iron-absorption process in the intestines

Front 399

Failure of the iron-absorption process in the intestines can lead to total body iron accumulations in the range of _____ to _______ grams, compared with normal iron stores of _____ to ______ grams.

Back 399

(1) 60 to 80 grams
(2) 4.5 to 5 grams

Front 400

What type of damage is excessive accumulations of rion associated with?

Back 400

liver and pancreatic cell damage

Front 401

Give an example of disease caused by iron overload?

Back 401

hemochromatosis, a genetic disorder of iron metabolism

Front 402

What is bilirubin?

Back 402

a normal, yellow-to-green pigment of bile derived from the porphyrin structure of hemoglobin

Front 403

What does excess bilirubin in cells and tissues cause?

Back 403

jaundice (icterus), or yellowing of the skin

Front 404

When does jaundice occur?

Back 404

when the bilirubin levels exceed 1.5 to 2 mg/dl of plasma

Front 405

What are normal levels of bilirubin?

Back 405

0.4 to 1 mg/dl

Front 406

When does hyperbilirubinemia occur?

Back 406

with (1) destruction of RBCs, such as hemolytic jaundice, (2) disease affecting the metabolism and excretion of bilirubin in the liver; and (3) diseases that cause obstruction of the common bile duct, such as gallstones or pancreatic tumors

Front 407

What drugs can obstruct the normal flow of bile through the liver?

Back 407

certain drugs (esp. chlorpromazine and other phenothiazine derivatives), estrogenic hormones, and halothane, an anesthetic

Front 408

Where do calcium salts accumulate?

Back 408

in both injured and dead tissues

Front 409

List the mechanism of cellular calcification.

Back 409

(1) the influx of extracellular calcium in injured mitochondria
(2) excretion of acid in alveoli, gastric epithelium, and renal tubules leading to the local production of hydroxyl ions which cause calcium accumulation in these sites

Front 410

What do hydroxyl ions result in?

Back 410

the precipitation of calcium hydroxide (Ca[OH]^2) and hydroxyapatite (3Ca^3[PO^4]^2Ca[OH]^2), a mixed salt.

Front 411

When does damage caused by calcium occur?

Back 411

when calcium salts clump and harden, interferring with normal cellular structure and function

Front 412

Pathologic calcification can be _________ or _________.

Back 412

(1) dystrophic
(2) metastatic

Front 413

Where does dystrophic calcification occur?

Back 413

in dying and dead tissues, chronic tuberculosis of the lungs and lymph nodes, advanced atheroscelerosis (narrowing as a result of plaque accumulation), and heart valve injury

Front 414

What does calcification of the heart valves do?

Back 414

interferes with their opening and closing, causing heart murmurs

Front 415

What does calcification of the coronary arteries predispose them to?

Back 415

severe narrowing and thrombosis, which can lead to myocardial infarction

Front 416

How do the center of tumors become calcified?

Back 416

over time, the center is deprived of its oxygen supply, dies, and becomes calcified.

Front 417

What do the calcium salts appear as in the centers of tumors?

Back 417

as gritty, clumped granules that can become hard as stone. When several layers clump together, they resemble grains of sand and are called psammoma bodies.

Front 418

What does metastatic calcification consist of?

Back 418

mineral deposits that occur in undamaged normal tissues as the result of hypercalcemia (excess calcium in the blood)

Front 419

What conditions cause hypercalcemia?

Back 419

hyperparathyroidism
toxic levels of vitamin D
hyperthyroidism
idiopathic hypercalcemia of infancy
Addison disease (adrenocortical insufficiency)
systemic sarcoidosis
milk-alkali syndrome
increased bone demineralization that results from bone tumors, leukemia, and disseminated cancers

may also occur in advanced renal failure with phosphate retention, resulting in hyperparathyroidism

Front 420

What is the major end product of purine catabolism in the absence of urate oxidase, in humans?

Back 420

uric acid (urate)

Front 421

What are the levels of stable serum urate concentration in postpubertal males? Females?

Back 421

Males: 5 mg/dl
Females: 4 mg/dl

Front 422

What do disturbances in maintaining serum urate levels result in?

Back 422

hyperuricemia and the deposition of sodium urate crystals in the tissues, leading to painful disorders collectively called gout

Front 423

What disorders are included in gout?

Back 423

acute arthritis
chronic gouty arthritis
tophi (firm, nodular, subcutaneous deposits of urate crystals surround by fibrosis), and nephritis (inflammation of the nephron)

Front 424

What does chronic hyperuricemia result in?

Back 424

the deposition of urate in tissues, cell injury, and inflammation

Front 425

Why do urate crystals persist in dead cells?

Back 425

because they are not degraded by lysosomal enzymes

Front 426

What are the systemic manifestations of cellular injury?

Back 426

a general sense of fatigue and malaise, a loss of well-being, and altered appetite

fever is often present because of biochemicals produced during the inflammatory response

Front 427

What causes fever?

Back 427

release of endogenous pyrogens (interleukin-1, TNF-alpha, prostaglandins) from bacteria or macrophages; acute inflammatory response

Front 428

What causes increased heart rate?

Back 428

increase in oxidative metabolic processes resulting from fever

Front 429

What causes an increase in leukocytes (leukocytosis)?

Back 429

increase in total number of white blood cells because of infection; normal is 5000-9000/mm^3 (increase is directly related to the severity of the infection)

Front 430

What causes pain?

Back 430

various mechanisms, such as release of bradykinins, obstruction, pressure

Front 431

What causes the presence of cellular enzymes?

Back 431

release of enzymes from cells of tissue* in extracellular fluid

Front 432

What causes the presence of lactate dehydrogenase (LDH) (LDH isoenzymes)?

Back 432

release from red blood cells, liver, kidney, skeletal muscle

Front 433

What causes the presence of creatine kinase (CK) (CK isoenzymes)?

Back 433

release from skeletal muscle, brain, heart

Front 434

What causes the presence of aspartate aminotransferase (AST/SGOT)?

Back 434

release from heart, liver, skeletal muscle, kidney, pancreas

Front 435

What causes the presence of alanine aminotransferase (ALT/SGPT)?

Back 435

release from liver, heart, kidney

Front 436

What causes the presence of alkaline phosphatase (ALT)?

Back 436

release from liver, bone

Front 437

What causes the presence of amylase?

Back 437

release from pancreas

Front 438

What causes the presence of aldolase?

Back 438

release from skeletal muscle, heart

Front 439

What does cellular death eventually lead to?

Back 439

cellular dissolution, or necrosis

Front 440

What is necrosis?

Back 440

the sum of cellular changes after local cell death and the process of cellular self-digestion known as autodigestion, or autolysis

Front 441

What are the structural signs that indicate irreversible injury and progression to necrosis?

Back 441

dense clumping and progressive disruption of genetic material and disruption of the plasma and organelle membranes

Front 442

What is karyolysis?

Back 442

nuclear dissolution and lysis of chromatin from the action of hydrolytic enzymes

Front 443

What is pyknosis?

Back 443

when the nucleus shrinks and becomes a small, dense mass of genetic material, which eventually dissolves by karyolysis as a result of the action of hydrolytic lysosomal enzymes on DNA

Front 444

What does karyorrhexis mean?

Back 444

fragmentation of the nucleus into smaller particles or "nuclear dust."

Front 445

What are the 4 major types of necroses?

Back 445

(1) coagulative
(2) liquefactive
(3) caseous
(4) fatty

Front 446

What is another type of necrosis that is not considered a distinctive type?

Back 446

gangrenous necrosis

Front 447

Where does coagulative necrosis primarily occur?

Back 447

(1) kidneys
(2) heart
(3) adrenal glands

Front 448

What does coagulative necrosis commonly result from?

Back 448

hypoxia caused by severe ischemia or hypoxia caused by chemical injury, especially ingestion of mercuric chloride

Front 449

What is coagulation caused by?

Back 449

protein denaturation, which causes the protein albumin to change from a gelatinous, transparent state to a firm, opaque state

Front 450

What does liquefactive necrosis commonly result from?

Back 450

ischemic injury to neurons and glial cells in the brain

Front 451

Why is dead brain tissue readily affected by liquefactive necrosis?

Back 451

because brain cells are rich in the digestive hydrolytic enzymes and lipids and the brain contains little connective tissue

Front 452

How is dead brain tissue destroyed?

Back 452

cells are digested by their own hydrolases, so the tissue becomes soft, liquefies, and is walled off from healthy tissue, forming cysts.

Front 453

What can cause brain tissue to die and be walled off from healthy tissue by cyst formation?

Back 453

bacterial infection, esp. staphylococci, streptococci, and Escherichia coli

Front 454

What does caseous necrosis usually result from?

Back 454

tuberculous pulmonary infection, esp. by Mycobacterium tuberculosis.

Front 455

What is caseous necrosis a combination of?

Back 455

coagulative and liquefactive necroses

Front 456

Describe the process of caseous necrosis.

Back 456

dead cells disintegrate, but the debris is not completely digested by the hydrolases. Tissues resemble clumped cheese in that they are soft and granular. A granulomatous inflammatory wall encloses areas of caseous necrosis.

Front 457

What is fat necrosis?

Back 457

cellular dissolution caused by powerful enzymes, called lipases, that occur in the breast, pancreas, and other abdominal structures.

Front 458

What do lipases do?

Back 458

break down triglycerides, releasing free fatty acids, which then combine with calcium, magnesium, and sodium ions, creating soaps (saponification).

Front 459

Describe the appearance of fatty necrotic tissue.

Back 459

opaque and chalk-white

Front 460

What does gangrenous necrosis refer to?

Back 460

death of tissue

Front 461

What does gangrenous necrosis result from?

Back 461

severe hypoxic injury, commonly occurring because of arteriosclerosis, or blockage, of major arteries, particularly those in the lower leg

Front 462

What is dry gangrene usually the result of?

Back 462

coagulative necrosis

Front 463

What are the characteristics of dry gangrene?

Back 463

the skin becomes very dry and shrinks, resulting in wrinkles, and its color changes to dark brown or black

Front 464

When does wet gangrene develop?

Back 464

when neutrophils invade the site, causing liquefactive necrosis.

Front 465

Where does wet gangrene usually develop?

Back 465

in internal organs

Front 466

What are the characteristics of wet gangrene?

Back 466

the site becomes cold, swollen, and black

a foul odor is present, and if systemic symptoms become severe, death can ensue

Front 467

What is gas gangrene?

Back 467

a special type of gangrene caused by infection of injured tissue by one of many species of Clostridium

Front 468

What do Clostridium bacteria produce?

Back 468

hydrolytic enzymes and toxins that destroy connective tissue and cellular membranes and cause bubbles of gas to form in muscle cells

Front 469

What causes gas gangrene to be fatal?

Back 469

if enzymes lyse the membranes of red blood cells, destroying their oxygen-carrying capacity.

Death is caused by shock.

Front 470

In gas gangrene, what is death caused by?

Back 470

shock

Front 471

What is apoptosis?

Back 471

an active process of cellular self-destruction called programmed cell death--that is, cells need to die otherwise endless proliferation would lead to gigantic bodies

Front 472

How many new cells does the average human create in a day?

Back 472

about 10 billion new cells, and kill off the same number

Front 473

What are the activated genes that cause apoptosis called? Why?

Back 473

suicide cells

because their activation by the nucleus inactivates so-called life-sustaining genes and promotes pathways leading to killer genes

Front 474

What cells does apoptosis affect?

Back 474

scattered, single cells; although there are examples of it occurring in widespread areas

Front 475

Describe the process of apoptosis.

Back 475

nuclear and cytoplasmic shrinkage of a cell followed by fragmentation into membrane-bound fragments and subsequent phagocytosis by neutrophils from neighboring healthy cells

Front 476

What does apoptosis determine?

Back 476

the size, patterning, and function of many tissues

Front 477

How can apoptosis be activated exogenously?

Back 477

by exogenous factors such as a long-lasting viral infection

Front 478

How can apoptosis be activated endogenously?

Back 478

by the absence of certain growth factors

Front 479

What is physiologic apoptosis important in?

Back 479

in the development of body tissues

for example, it is responsible for local deletion of cells during tissue turnover and normal embryonic development. It has been shown to occur in endocrine-dependent tissues undergoing normal atrophic change

Front 480

What is pathologic apoptosis the result of?

Back 480

intracellular events or adverse exogenous stimuli.

for example, deficiencies of specific enzymes can lead to disease where cells have undergone apoptosis.

liver cells infected with viral hepatitis C, for example, can undergo apoptosis

Front 481

What has apoptosis in hemopoietic cells been linked to?

Back 481

the production of free radicals and can spontaneously occur in some malignant tumors and cells treated with ionizing radiation and chemotherapy.

Front 482

What can absence of apoptosis cause?

Back 482

pathologic change

a mutaton in a gene (bcl-2, for example) that promotes apoptosis may only give the signal to proliferate and not die. Thus, lymphocytes may accumulate, enlarging lymph nodes and eventually proliferating into the blood.

Front 483

What is the best cellular marker for apoptosis?

Back 483

karyohexis (fragmentation of the nucleus to dust), especially in an isolated cell

Front 484

What is aging usually defined as?

Back 484

a normal physiologic process that is both universal and inevitable

Front 485

What do the basic mechanisms of aging depend on?

Back 485

the irreversible and universal processes at the cellular and molecular level

Front 486

What is the maximal life span in humans?

Back 486

between 80 and 100 years and does not vary significantly among populations

Front 487

Why has the death rate for people aged 65 years and older declined?

Back 487

largely as a result of decreased cardiovascular disease

Front 488

What is life expectancy?

Back 488

a summary measure of mortality--the average number of years of life expected if current death rates were constant.

Front 489

In 2004 what was the life expectancy at birth for the total population?

Back 489

77.9 years

Front 490

What was the gender gap between male and female life expectancy in 2004?

Back 490

5.2 years, down from 5.4 years in 2002

Front 491

What is the life expectancy of a male? Female?

Back 491

Male: 75 years
Females: 80 years

Front 492

Which state in the US had the lowest mortality rate in 2004?

Back 492

Hawaii: 650.1 deaths/100,000

Front 493

Which state in the US had the highest mortality rate in 2004?

Back 493

Mississippi: 1015.2 deaths/100,000

Front 494

Which country ranks numer 1 for life expectancy (males, 82.8 years; females 87.7 years)?

Back 494

Japan

Front 495

What are some of the prominent theories of aging?

Back 495

(1) cellular changes produced by genetic and environmental-lifestyle factors; (2) changes in cellular regulatory, or control, mechanisms, esp. in cells of the neuro-endocrine, immune, and central nervous systems; and (3) degenerative extracellular and vascular alterations

Front 496

How might genetic and environmental factors contribute to the aging process?

Back 496

cells may become damaged during replication as a result of factors within the cell, such as DNA and protein mechanisms, or factors outside of the cell, such as ionizing radiation

cells may already be programmed at birth or injured during life so as to cause errors in mitotic division and in replication of genetic material, eventually leading to either cellular atrophy or death

genetic mechanism: programmed aging--some investigators think that each normal cell may have a finite life span during which it can replicate

somatic mutation hypothesis--proposes that aging is the result of DNA damage, inefficiency of repair, and loss of integrity of DNA synthesis

catastrophic or error-prone theory--stated that the presence of errors in those enzymes involved in transcription and translation, and thus their own synthesis, leads to an increase in errors and eventually to the death of the cell

Front 497

Where is cellular atrophy most common?

Back 497

in the thymus, testis, ovary, uterus, and breast

Front 498

How might alterations in cellular control mechanisms cause aging?

Back 498

neuroendocrine theory--purports that a genetic program for aging is encoded in the brain and is controlled and relayed to peripheral tissues through hormonal agents. Possible mechanisms include: (1) increased hormonal degradation, (2) decreased rate of hormonal synthesis and secretion; and (3) decreased target-organ sensitivity related to a number of cellular receptors for hormonal ligands, ligand-receptor binding, or ligand internalization

proponents of immune theories of aging believe that the immune system is implicated in aging because (1) immune function declines with age; (2) the decline in immune function is related to certain diseases, such as cancer, and to many other secondary effects; and (3) the number of auto-antibodies (antibodies that attack body tissues) increases with age

Front 499

How might the extracellular environment be associated with the aging process?

Back 499

the binding of collagen; the increase in free radicals' effects on cells; the structural alterations of fascia, tendons, ligaments, bones, and joints; and peripheral vascular disease, particularly arteriosclerosis

affects the extracellular matrix with increased cross-linking, decreased synthesis, and increased degradation of collagen

skeletal muscle alterations, cataracts, diverticula, hernias, and rupture of intervertebral disks

free radicals of oxygen damage tissues during the aging process

with aging, lipid, calcium, and plasma proteins are deposited in the walls of vessels. These depositions cause serious basement membrane thickening and alterations in smooth muscle functioning, resulting in arteriosclerosis

Front 500

What is arteriosclerosis?

Back 500

a progressive disease that causes such problems as stroke, myocaridal infarction, renal disease, and peripheral vascular disease

Front 501

What happens to cells as they age?

Back 501

atrophy, decreased function, and loss of cells, possibly caused by apoptosis

Front 502

What does loss of cellular function initiate?

Back 502

the compensatory mechanisms of hypertrophy and hyperplasia of remaining cells, which can lead to metaplasia, dysplasia, and neoplasia.

All of these changes can alter receptor placement and function, nutrient pathways, secretion of cellular products, and neuroendocrine control mechanisms

Front 503

In the aged cell, what are most susceptible to injurious stimuli?

Back 503

DNA, RNA, cellular proteins, and membranes

Front 504

What type of injuries can occur to DNA?

Back 504

breaks, deletions, and additions

Front 505

What does lack of DNA repair increase?

Back 505

the cell's susceptibility to mutations that may be lethal or may promote the development of neoplasia

Front 506

What is the most characteristic tissue change with age?

Back 506

a progressive stiffness or rigidity that affects many systems, including the arterial, pulmonary, and musculoskeletal systems

Front 507

What is the consequence of blood vessel and organ stiffness?

Back 507

a progressive increase in peripheral resistance to blood flow

Front 508

Aging occurs in part because of the declines in the function of ___________.

Back 508

tissue stem cells

Front 509

What does normal tissue function require?

Back 509

that the rate of cell loss be matched by the rate of cell renewal.

Aging is increased by changes that either accelerates cellular loss or slows tissue repair.

Front 510

What do changes in the endocrine and immune systems include?

Back 510

thymus atrophy

Front 511

What type of atrophy occurs in puberty?

Back 511

thymus atrophy, causing a decreased immune response to T-dependent antigens (foreign proteins), increased autoantibodies and immune complexes (antibodies bound to antigens) and an overall decrease in the immunologic tolerance for the host's own cells further diminish the effectiveness of the immune system later in life

Front 512

In women, the reproductive system loses _______, and in men, __________ decreases. Responsiveness to ___________ decreases in the ________ and __________.

Back 512

(1) ova
(2) spermatogenesis
(3) hormones
(4) breast
(5) endometrium

Front 513

How does aging affect the stomach?

Back 513

decreases the rate of emptying and secretion of hormones and hydrochloric acid

Front 514

What does muscular atrophy do?

Back 514

diminishes mobility by decreasing motor tone and contractility

Front 515

What is sarcopenia?

Back 515

loss of muscle mass

Front 516

How is the skin of the aged individual affected?

Back 516

atrophy and wrinkling of the epidermis and alterations in underlying dermis, fat, and muscle

Front 517

What total body changes occur in aging?

Back 517

(1) decrease in height
(2) reduction in circumference of the neck, thighs, and arms
(3) widening of the pelvis
(4) lengthing of the nose and ears

Front 518

What are several of the total body changes the result of?

Back 518

tissue atrophy and decreased bone mass caused by osteoporosis and osteoarthritis

Front 519

How does body compositon change with age?

Back 519

with middle age, there is an increase in body weight (men gain until 50 year of age and women gain until 70 years) and fat mass, followed by a decrease in stature, weight, fat-free mass, and body cell mass at older ages.

Front 520

As fat ________, total body water ____________.

Back 520

(1) increases
(2) decreases

Front 521

What symptoms of aging are associated with non-insulin dependent diabetes and heart disease?

Back 521

(1) increased body fat
(2) centralized fat distribution (abdominal)

Front 522

What does an increased sodium/potassium ratio suggest?

Back 522

that the decreased cellular mass is accompanied by an increased extracellular fluid compartment

Front 523

What is frailty?

Back 523

a wasting syndrome of aging, leaving a person vulnerable to falls, functional decline, disease, and death

Front 524

What are thought to be important determinants of frailty?

Back 524

age-related changes in teh musculoskeletal system

Front 525

What are the criteria to define frailty?

Back 525

mobility
balance
muscle strength
motor activity
cognition
nutritional status
endurance
falls
fractures
bone density

Front 526

What does age-related endocrine-immune dysregulation include?

Back 526

declining hormones (for ex., estrogens, testosterone, IGF-1), and increasing proinflammatory cytokines (for ex., IL-6 and C-reactive protein [CRP])

Front 527

What are the joint effects of low levels of IGF-1 and increased levels of IL-6 related to?

Back 527

high risk for progressive disability and death in older women

Front 528

Elevated levels of what cytokines have been related to sarcopenia?

Back 528

catabolic cytokines including TNF-alpha, as well as IL-6

Front 529

What may declines in ovarian function lead to?

Back 529

increased proinflammatory cytokines (such as IL-1, IL-6, and TNF-alpha)

Front 530

The endocrine-immune dysregulation may be an important mechanism of what?

Back 530

frailty

Front 531

What is somatic death?

Back 531

death of the entire person

Front 532

How is postmortem change different than the changes that follow cellular death in a live body?

Back 532

postmortem change is diffuse and does not involve components of the inflammatory response.

Front 533

What are the most notable manifestations that death of the person has occurred?

Back 533

complete cessation of respiration and circulation

the surface of the skin usually becomes pale and yellowish; however, the lifelike color of the cheeks and lips may persist after death that is caused by CO poisoning, drowning, or chloroform poisoning

Front 534

What happens to body temperature after death?

Back 534

it falls gradually immediately after death and then more rapidly (approx. 1.0* to 1.5* F/hr) until, after 24 hours, body temperature equals that of the environment

Front 535

What happens to body temperature after death caused by certain infective diseases?

Back 535

body temperature may continue to rise for a short time

Front 536

What is postmortem reduction of body temperature called?

Back 536

algor mortis

Front 537

What happens to blood pressure in the retinal vessels after death?

Back 537

it decreases, causing muscle tension to decrease and the pupils to dilate. The face, nose, and chin become sharp or peaked-looking as blood and fluids drain away.

Front 538

What is gravity's effect on blood after death?

Back 538

it causes the blood to settle in the most dependent, or lowest, tissues, which develop a deep purple discoloration called livor mortis

Front 539

What is livor mortis?

Back 539

a deep purple discoloration in the tissues from settling blood

Front 540

What happens within 6 hours after death?

Back 540

acidic compounds accumulate within the muscles because of the breakdown of carbohydrate and depletion of ATP. This interferes with ATP-dependent detachment of myosin from actin (contractile proteins), and muscle stiffening, or rigor mortis, sets in.

Front 541

What is rigor mortis?

Back 541

muscle stiffening

Front 542

What muscles are usually affected by rigor mortis first?

Back 542

small muscles, particularly the muscles of the jaw

Front 543

How long after death does rigor mortis affect the entire body?

Back 543

within 12 to 14 hours

Front 544

When are the signs of putrefaction obvious?

Back 544

about 24 to 48 hours after death

Front 545

When does rigor mortis diminish causing the body to become flaccid?

Back 545

at 36 to 62 hours

Front 546

What is the most visible putrefaction change?

Back 546

a greenish discoloration of the skin, particularly the abdomen

Front 547

What is the greenish coloration of putrefaction though to be related to?

Back 547

the diffusion of hemolyzed blood into the tissues and the production of sulfhemoglobin

Front 548

What occurs at the same time as putrefaction?

Back 548

slippage or loosening of the skin from underlying tissues

Front 549

What occurs after the skin loosens from underlying tissues?

Back 549

swelling or bloating of the body and liquefactive changes occur, sometimes causing opening of the body cavities

Front 550

At the microscopic level, what are the putrefactive changes associated with?

Back 550

the release of enzymes and lytic dissolution called postmortem autolysis