Chapter 4 Lecture

Question 1

adaptation

Answer 1

ways cells get injuried

if injury is so extensive then we have death-nercrosis and apotsis

Question 2

Atrophy

Answer 2

Decrease in cellular size

disuse phenomenon

ex. someone paralayzed or bed rest

Question 3

Hypertrophy

when it becomes pathogenic.. give ex, only works for awhile

Answer 3

Increase in cellular size

heart failure, MI scarring and damage to left ventricle, as that damage weaker the contract, as an adapative mechanisms that wall will thicken, cells will hypertophy,

Question 4

Hyperplasia

Answer 4

Increase in number of cells

Question 5

Dysplasia-adaptation

cervical dyplasia

Answer 5

Deranged cellular growth

-could turn into cancer

Question 6

Metaplasia-adaptation

Answer 6

Replacement of one type of cell with another

Question 7

Physiologic (adaptive) vs. pathogenic

Answer 7

adaptive-normal

extensive-pathogenic cells aren’t going to work right anymore

Question 8

Cellular Injury
Reversible?
Irreversible?
example

Answer 8

Occurs if cell unable to maintain homeostasis

reversible-cells recover
irreversible-cells die

CPR

Question 9

The injury is reversible if it is mild or transient, but if the stimulus persists

Answer 9

the cell suffers irreversible injury and eventually death.

Question 10

The normal cell responds to physiologic and pathologic stresses by

Answer 10

adapting (atrophy, hypertrophy, hyperplasia, metaplasia).

Question 11

Hypoxic injury

results from?

Answer 11

Reduced amount of oxygen in the air

• Loss of hemoglobin or decreased efficacy of hemoglobin
• Decreased production of red blood cells
• Diseases of the respiratory and cardiovascular systems
• Poisoning of the oxidative enzymes (cytochromes) within the cells

Question 12

Single most common cause of cellular injury

Answer 12

hypoxia

Question 13

Ischemia

Answer 13

most common cause of hypoxia

blood clot, compressions

decreased blood supply

Question 14

Hypoxic injury

Answer 14

Hypoxia decreased O2 w/in cells
Ischemia-low blood supply
Hypoxemia- low o2 in blood

Question 15

Hypoxic Injury Induced by Ischemia

Answer 15

Consequences of decreased oxygen delivery or ischemia with decreased ATP

The structural and physiologic changes are reversible if oxygen is delivered quickly. Significant decreases in ATP result in cell death, mostly by necrosis.

membranes of the mitochondria are proteins that can activate the cell’s suicide pathways, called apoptosis.

C,Calcium ions are critical mediators of cell injury. Calcium ions are usually maintained at low concentrations in the cell’s cytoplasm

thus ischemia and certain toxins can initially cause an increase in the release of Ca++from intracellular stores and later an increased movement (influx) across the plasma membrane.

Question 16

Hypoxic injury (Cont.)

what is anoxia?

what are some cellular responses? of hypoxic injury

Answer 16

Anoxia (an absence of oxygen)

Cellular responses:
Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange
Cellular swelling
Vacuolation

Question 17

Hypoxic injury (Cont.)
Ischemia-reperfusion injury

Mechanisms:

Answer 17

Additional injury that can be caused by restoration of blood flow and oxygen

anything that restricts blood flow

Oxidative stress
Increased intracellular calcium
Inflammation
Complement activation

Question 18

Reperfusion Injury.

Answer 18

Without oxygen, or anoxia, the cells display hypoxic injury and become swollen. With reoxygenation, reperfusion injury increases because of the formation of reactive oxygen radicals that can cause cell necrosis.

blood flow back
can make more problems

Question 19

ROS- another mecahnism besides hypoxic injuiry

Answer 19

Free radicals and reactive oxygen species (ROS) – build up as a result of oxidative stress

Question 20

connection between ROS’s and electrons antioxidants

causes damage in 4 ways from a build up of ROS

Answer 20

Electrically uncharged atom or group of atoms having an unpaired electron that damage:

• MAJOR ENERGY SOURCES
• Lipid peroxidation- alteration in fat, proteins
• Alteration of proteins
• Alteration of DNA
• Mitochondria(hypoxia and ROS)

Question 21

The Role of Reactive Oxygen Species (ROS) in Cell Injury.

Answer 21

• cell stressors
• radiation, toxins, and reperfusion of oxygen.

Free radicals are removed by normal decay and enzymatic systems.

Question 22

ROS accumulates in cells because

Answer 22

of insufficient removal or excess production leading to cell injury, including lipid peroxidation, protein modifications, and DNA damage or mutations.

Question 23

Cellular Injury Mechanisms - the 3

Answer 23

hypoxia
ros’s
cellular

Question 24

Cellular Injury Mechanisms

Chemical injury

Xenobiotics

usually affects the

lead:

Carbon monoxide:

Answer 24

esp. harmful to liver which metabolizes xenobiotics

liver

lead:Heavy metal, alters cellular messenging capability, especially in the CNS (cognitive deficits, behavioral changes)

carbon monoxide:oxygen deprivation by binding with hemoglobin
CO and other components of air pollution generate inflammation, trigger oxidative stress, induce mitochondrial dysfunction and cellular death by necrosis or apoptosis

Question 25

Chemical injury/ethanol Mercury

Answer 25

Toxic effects of acetaldehyde, a metabolic byproduct Rhabdomyolysis (breakdown of muscle tissue with release of myoglobin component Mercury:alteration of cell membrane permeab ility, damages cellular DNA

Question 26

Cellular Injury Mechanisms (Cont.) | Chemical agents including drugs

Answer 26

- Over-the-counter and prescribed drugs - Leading cause of child poisoning -Direct damage Tylenol- can injure directly, can trigger hypersensitive reaction -Hypersensitivity reactions

Question 27

Cellular Injury Mechanisms (Cont.) Chemical agents including drugs Direct damage

Answer 27

Chemicals and drugs injure cells by combining directly with critical molecular substances Chemotherapeutic drugs Drugs of abuse

Question 28

Cellular Injury Mechanisms (Cont.) Chemical agents including drugs -Hypersensitivity reactions

Answer 28

Range from mild skin rashes to immune-mediated organ failure

Question 29

Chemical Liver Injury. Liver injury is a result of genetic, environmental, biologic, and dietary factors.

Answer 29

Certain chemicals can form toxic or chemically reactive metabolites. The risk of liver injury also can increase with increasing doses of a toxicant. Xenobiotic enzyme induction can lead to altered metabolism of chemicals, and drugs can either inhibit or induce drug-metabolizing enzymes. These changes can lead to greater toxicity. The dose at the site of action is controlled by the Phase I to III xenobiotic metabolites and metabolizing enzymes are encoded by numerous different genes. Therefore, the metabolism and toxicity outcomes can vary greatly among individuals. Additionally, all aspects of xenobiotic metabolism are regulated by certain transcription factors (cellular mediators of gene regulation). Overall, the extent of cell damage depends on the balance between reactive chemical species and protective responses aimed at decreasing oxidative stress, repairing macromolecular damage, or preserving cell health by inducing apoptosis or cell death. Significant clinical outcomes of chemical-induced liver injury occur with necrosis and the immune response.

Question 30

Unintentional and Intentional Injuries (4) more common among?

Answer 30

More common among men and higher rates among blacks -Blunt force injuries Result of application of mechanical force to body Results in tearing, shearing, or crushing of tissues Motor vehicle accidents and falls -Contusions -Lacerations -Fractures

Question 31

-Blunt force injuries

Answer 31

Result of application of mechanical force to body Results in tearing, shearing, or crushing of tissues Motor vehicle accidents and falls

Question 32

``` Unintentional and Intentional Injuries (Cont.) Sharp force injuries Gunshot wounds (entry/exit point) ```

Answer 32

Incised wound Stab wound Puncture wound Chopping wound

Question 33

Unintentional and Intentional Injuries (Cont.) Asphyxial injuries: caused by?

Answer 33

-Caused by a failure of cells to receive or use oxygen -Suffocation -Choking asphyxiation -Strangulation -Hanging, ligature, and manual strangulation -Chemical asphyxiants -Cyanide and hydrogen sulfide Drowning

Question 34

Infectious Injury (5) Disease-producing potential 3 points

Answer 34

-Pathogenicity damage (virulence, or infectivity) of a microorganism Disease-producing potential Invasion and destruction Toxin production Production of hypersensitivity reactions

Question 35

Asphyxial injuries: because of hypoxia

Answer 35

is a condition of severely deficient supply of oxygen to the body that arises from abnormal breathing. -Caused by a failure of cells to receive or use oxygen ``` -Suffocation Choking asphyxiation -Strangulation Hanging, ligature, and manual strangulation -Chemical asphyxiants -Cyanide and hydrogen sulfide -Drowning ```

Question 36

Infectious Injury

Answer 36

Pathogenicity damage (virulence, or infectivity) of a microorganism Disease-producing potential Invasion and destruction Toxin production Production of hypersensitivity reactions

Question 37

Immunologic and Inflammatory Injury there's three what are they?

Answer 37

Phagocytic cells Immune and inflammatory substances -Histamine, antibodies, lymphokines, complement, and proteases Membrane alterations - Potassium leakage out of cell, water influx into cell - Competitive binding of antibodies to receptor molecules on plasma membrane

Question 38

Thermal Injury and Sun Exposure Thermal injury

Answer 38

Thermal injury - localized heat stress, acute burn trauma DNA damage resulting in cell death Heat-injured cells signal to surrounding cells which can also experience the same impacts

Question 39

Thermal Injury and Sun Exposure Sun Exposure

Answer 39

Sun exposure UV light generates free radicals that damage cellular DNA even after sun exposure has terminated DNA damage can trigger malignant changes in skin cells

Question 40

Manifestations of Cellular Injury Cellular **accumulations** (infiltrations): can cause more cellular injury- cascade effect what factors can change?

Answer 40

Water-cellular swelling oncosis sodium Lipids and carbohydrates- cause damage cause neuro conditions/damage Glycogen-changes the whole glucose energy levels Proteins- accumulate in kidney protein damages tubule and cause acute renal failure

Question 41

Manifestations of Cellular Injury (Cont.) Cellular accumulations (infiltrations): (Cont.) Pigments describe pigments, calcium and urate

Answer 41

Cellular accumulations (infiltrations): (Cont.) Pigments Melanin, hemoproteins, bilirubin Calcium-damage cell membrane, cell nucleus Dystrophic Metastatic Urate- occur in metabolic coniditon called gaut, get deposited in joiunts and cause aithristis

Question 42

– Necrosis or Apoptosis

Answer 42

apoptosis-self death necrosis: cell is dying off-necrosis, changes in cell after it dies, autodigestion process,Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis)

Question 43

Coagulative necrosis

Answer 43

Kidneys, heart, and adrenal glands Protein denaturation  Coagulative necrosis. A wedge-shaped kidney infarct (yellow). 

Question 44

Liquefactive necrosis

Answer 44

Neurons and glial cells of the brain Hydrolytic enzymes Bacterial infection Staphylococci, Streptococci, and Escherichia coli Liquefactive necrosis of the brain. The area of infarction is softened as a result of liquefaction necrosis

Question 45

Caseous necrosis

Answer 45

 Caseous necrosis. Tuberculosis of the lung, with a large area of caseous necrosis containing yellow-white and cheesy debris. Tuberculous pulmonary infection Combination of coagulative and liquefactive necrosis

Question 46

Fat necrosis

Answer 46

Breast, pancreas, and other abdominal organs Action of lipases -fatty enzymes in there organs, as a reult triglyc. are broken down and fatty acids are released Fat necrosis of pancreas. Interlobular adipocytes are necrotic; acute inflammatory cells surround these chalky apperance

Question 47

Gangrenous necrosis

Answer 47

large amount of tissue is dead Death of tissue from severe hypoxic injury Dry-shrink-turn black vs. wet gangrene, damp liquifies Gas gangrene, Clostridium In certain circumstances, necrotic tissue will be invaded by putrefactive organisms that are both saccharolytic and proteolytic. Foul-smelling gases are produced, and the tissue becomes green or black as a result of breakdown of hemoglobin. Obstruction of the blood supply to the bowel almost inevitably is followed by gangrene. 

Question 48

Apoptosis

Answer 48

Programmed cellular death | occurs in undamaged death

Question 49

Apoptosis | Physiologic vs. pathologic

Answer 49

Physiologic, because cells need to die Pathologic,disregulated process in response to Severe cell injury Build-up of abnormal (“mis-folded”) proteins because of genetic mutations or free radicals Infections Obstruction of ducts in organs such as pancreas and kidney

Question 50

Mechanisms of Apoptosis.

Answer 50

The two pathways of apoptosis differ in their induction and regulation, and both culminate in the activation of “executioner” caspases. The induction of apoptosis by the mitochondrial pathway involves the Bcl-2 family, which causes leakage of mitochondrial proteins. The regulators of the death receptor pathway involve the proteases, called caspases. (Adapted from Kumar V et al, editors: Robbins and Cotran pathologic basis of disease, ed 9, Philadelphia, 2015, Elsevier.

Question 51

Aging, a process vs. life span, time from birth to death | wear/tear

Answer 51

Maximal life span | Life expectancy – varies by gender and race-ethnicity

Question 52

Intracellular changes | wear/tear

Answer 52

Progressive shortening of telomeres in continuously-dividing cells Accumulation of cellular mutations

Question 53

Degenerative extracellular changes | wear/tear

Answer 53

Advanced glycation end-products induce cross-linking of proteins in collagen Cumulative cellular damage from effects of free radical that accumulate due to oxidative stress (e.g., malignant changes)

Question 54

Cellular aging USE IT OR LOSE IT Progressive stiffness and rigidity Sarcopenia ? Frailty syndrome

Answer 54

Atrophy, decreased function, and loss of cells Progressive stiffness and rigidity – blood vessels, ligaments, tendons Sarcopenia – decreased muscle mass and strength Mobility, balance, muscle strength, motor activity, cognition, nutrition, endurance, falls, fractures, and bone density

Question 55

``` Somatic Death Death of an entire person Postmortem changes: Algor mortis Livor mortis Rigor mortis, Postmortem autolysis with putrefaction ```

Answer 55

Algor mortis -Algor mortis is the change in body temperature following death. Livor mortis -When the heart stops functioning and is no longer agitating the blood, heavy red blood cells sink through the serum by action of gravity. Rigor mortis, Rigor mortis is one of the recognizable signs of death, caused by chemical changes in the muscles after death, causing the limbs of the corpse to stiffen.followed by flaccidity Postmortem autolysis with putrefaction the destruction of cells or tissues by their own enzymes, especially those released by lysosomes. Putrefaction is one of seven stages in the decomposition of the body of a dead animal. It can be viewed, in broad terms, as the decomposition of proteins in a process that results in the eventual breakdown of cohesion between tissues and the liquefaction of most organs.