Cell Injury, Death, and Adaptation

Question 1

Etiology categories of injurious agents causing cell injury/death/adaption

Answer 1

ATP depletion
Oxygen and oxygen-derived free radicals
Intracellular calcium and loss of calcium steady state
defects in membrane permeability

Question 2

Karyorrhexis

Answer 2

fragmentation of nuclear material

Question 3

Pyknosis

Answer 3

clumping of nuclear material

Question 4

Karyolysis

Answer 4

dissolution of nuclear material

Question 5

Cellular outcome of Na/K pump failure

Answer 5

Sodium ions enter freely (accompanied by water), potassium ions leave freely, and calcium ions gain abnormal entry into the cell and the intracellular organelles

When the cell swells, all of the organelles within the cell (which are also membrane-bound) swell
When the rough ER swells (where protein synthesis occurs), the ribosomes fall off and protein synthesis stops

Question 6

Cellular outcome of lactic acid buildup

Answer 6

Lactic acid buildup causes the intracellular pH to decline, incapacitating cells (which function within a very narrow range of pH)

Leads to: Pyknosis, karyorrhexis, and karyolysis and the rupture of already swollen lysosomes

Lysosomes release their proteolytic enzymes, which autodigest cell contents and the cell membrane
Disruption of the cell membrane increases calcium influx into the cell/organelles and causes release of cellular contents into the tissue spaces and blood (extracellular fluid)

Question 7

Results of excessive free intracellular calcium

Answer 7

This excessive free calcium activates proteases, endonucleases, and phospholipases that proceed to destroy the cell and its contents

Question 8

Reperfusion injuries

Answer 8

Occur when blood flow is restored to tissue that has been anoxic and functioning under anaerobic metabolism

Restoration of blood flow causes a burst of oxidative metabolism and accumulation of oxygen free radicals

Question 9

Free radicals

Answer 9

Unstable compounds with an unpaired electron in their outer ring, making them anxious to react with other substances

Normal byproducts of cellular metabolism that are always present in the body

Have a particular affinity for lipid substances

Question 10

Free radical effect on cell membranes

Answer 10

Free radicals combine avidly with cell or organelle membranes and “drill a hole”, or have a phosphokinase-like effect

This binding results in the dissolution of the membrane and chain reactions of toxic byproduct production, in an effect called lipid peroxidation

Question 11

Reactive oxygen species (ROS)

Answer 11

A subset of free radicals that contain oxygen (oxygen-based free radicals)

Formed as natural oxidant species in cells during mitochondrial respiration and ATP generation

Question 12

Free radical removal

Answer 12

antioxidants

Question 13

Endogenous agents

Answer 13

Normally found in the body

Question 14

Exogenous agents

Answer 14

Not normally found in the body

Question 15

Chronic alcoholism and lipids

Answer 15

increases the conversion of FFA to triglycerides

Question 16

Cause of liver fat accumulation

Answer 16

Increased mobilization and delivery of free fatty acids to liver cells can result in fat accumulation

Question 17

Unconjugated bilirubin

Answer 17

Fat-soluble and cannot be eliminated through the kidneys (urine)

Gradually released from macrophages into the plasma and combines with plasma albumin to transport to the liver

Taken up by liver cells and conjugated

Question 18

Conjugated bilirubin

Answer 18

Water-soluble and can be eliminated through urine

As the concentration of conjugated bilirubin in liver cells increases, it begins to diffuse out of the cell and into the blood (down its concentration gradient)

In addition, some of the conjugated bilirubin becomes part bile, which exits liver cells through the hepatic duct –> common bile duct –> into the duodenum

Once in the intestines, half of the conjugated bilirubin is converted by bacterial action into urobilinogen, which is highly soluble

In the feces, it becomes altered and oxidized to form stercobilin (gives stool brown color)

About 5% is excreted by the kidneys into the urine and becomes oxidized to urobilin (gives urine yellow color)

Question 19

Hemolytic jaundice

Answer 19

Excessive hgb breakdown and delivery of unconjugated bilirubin to the liver

Unconjugated bilirubin accumulates in plasma
Bilirubin absent in urine
Urobilinogen increased in urine and feces

Question 20

Hepatocellular jaundice

Answer 20

Liver disease state
Unable to uptake, conjugate, &/or excrete bilirubin

Severe elevation of serum bilirubin
Conjugated and unconjugated bilirubin in plasma
LFTs abnormal

Question 21

Obstructive jaundice

Answer 21

Obstruction to the flow of bile

Conjugated bilirubin accumulates in the liver and diffuses into the blood

Clay-colored stools (no bilirubin through intestines) and dark urine (how most of the conjugated bilirubin is excreted)

Question 22

Hyperbilirubinemia outcomes

Answer 22

CNS toxicity

Question 23

Kernicterus

Answer 23

significant neurological deficits or death due to hyperbilirubinemia

Question 24

Cell necrosis

Answer 24

Uncontrolled, irreversible cell injury and eventual cell death due to pathological processes

A pathologic, disorganized sequence of events that results in swelling of cell organelles, plasma membrane rupture, and eventual lysis of cells and stimulates the inflammatory process

Question 25

Coagulative necrosis

Answer 25

Most common type

Cell architecture remains preserved and tissue is usually replaced by scar/fibrous tissue

Gangrene is a subset (results from interruption of arterial blood supply to a tissue)

Question 26

Dry gangrene

Answer 26

An area is free of infection and in which the line of demarcation between live and dead tissue is apparent

Tissue undergoing dry gangrene becomes dry and shrunken (mummified)

Question 27

Wet gangrene

Answer 27

A combination of coagulative AND liquefactive necrosis

Infection is present in the area between live and dead tissue

The presence of an acute inflammatory reaction and inflammatory exudate are responsible for the “wet” component

Often malodorous, and the line of demarcation between live and dead tissue is unclear until the infection is arrested

Question 28

Gas gangrene

Answer 28

Wet gangrene caused by Clostridium perfringens, an organism that produces gas within the destroyed tissue

Question 29

Liquefactive gangrene

Answer 29

Most commonly observed in the CNS, and can occur in bacterial infections (pus)

Dying cells are digested by hydrolytic enzymes and lose their structural integrity, turning into a viscous mass

Formation of cysts

Question 30

Fat gangrene

Answer 30

Occurs in acute pancreatitis when pancreatic enzyme release leads to liquefaction of the fat cells in the peritoneal cavity

Saponification

Question 31

Caseous gangrene

Answer 31

“Cheesy”

Takes place in tuberculosis infection

Necrotic area is referred to as a granulom

Question 32

Apoptosis

Answer 32

Type I programmed cell death

Genetically controlled, but can be physiologic or pathologic

Initiated by activation of caspase enzymes

	○ Apoptosis components:
		§ Promoter: p53
		§ Bcl-2
		§ Apaf-1
		§ Caspase 9
                    § Cytochrome c

Eliminates individual cells, which are normally phagocytized

Not associated with inflammation

Question 33

Autophagy

Answer 33

Type II programmed cell death

A survival mechanism that salvages key metabolites to promote homeostasis (garbage collecting and recycling)

Question 34

Atrophy

Answer 34

A reduction in cell size and reversion to a lower and more efficient level of functioning

Occurs in response to a decrease in work demands or adverse environmental condition

Question 35

Hypertrophy

Answer 35

An increase in cell size and functional components within the cell resulting in an increase in tissue size

Occurs in response to an increase in work demands

Question 36

Hyperplasia

Answer 36

An increase in the number of cells in an organ or tissue that is still capable of mitotic division

Occurs in response to an increase in work demands

Question 37

Metaplasia

Answer 37

The substitution of one type of normal cell with another type of normal cell, but one that is not normally found in that tissue

The replacement cells are better able to survive under stressful circumstances

Often occurs in response to chronic irritation

Question 38

Dysplasia

Answer 38

Characterized by deranged cell growth and differentiation within a specific tissue, resulting in disorderly cells that vary in size, shape, and appearance

Preneoplastic

Question 39

Causes of aging

Answer 39

Thought to be a result of an accumulation of DNA and metabolic (free radical) damage

Cells may age more quickly when DNA repair mechanisms are faulty and when metabolic damage is excessive because of reduced antioxidants

Possible genetic, epigenetic, inflammatory, oxidative stress, and metabolic origins

Diet is thought to play a major role in the development of age-related disease

Associated with inflammation, hypercoagulability, and immune changes

May involve an increase in autoantibodies and damage accumulation

Question 40

Cross-linking theory of aging

Answer 40

Decrease in cell permeability