1 - Cell Injury & Death

Question 1

Define pathophysiology

Answer 1

study of disordered physiological processes associated with disease or injury

Question 2

Define Etiology

Answer 2

why = cause of disease

Question 3

Define pathogenesis

Answer 3

how = mechanisms of disease

Question 4

What are 8 causes of cell injury

Answer 4

• hypoxia (can lead to ischemia)
• ischemia
• toxins
• infectious microbes
• genetic abnormalities
• abnormal immune reactions
• nutritional imbalance
• physical agents

Question 5

What is ischemia?

Answer 5

absence/suppression of blood flow

decreased nutrients/O2 delivery

Question 6

What are the 2 most common cause of cell injury?

Answer 6

hypoxia and ischemia

Question 7

What are 3 causes of hypoxia?

Answer 7

• decreased blood supply
• decreased O2 carrying capacity of blood
• decreased ATP production via oxidative phosphorylation

Question 8

What is ischemia due to?

Answer 8

arterial blockage

Question 9

What does Cytochrome P450 do?

Answer 9

detoxifies the exogenous chemicals or converts them into active metabolites

Question 10

Where is Cytochrome P450 most active in?

Answer 10

endoplasmic reticulum of liver

Question 11

What are 5 examples of physical agents that can cause cell injury?

Answer 11

• mechanical trauma
• temperature extremes
• radiation
• electric shock
• sudden changes in atmospheric pressure

Question 12

What is the sequence of events in cell injury?

Answer 12

healthy cell @ homeostasis&raquo_space; injurious stimulus&raquo_space; REversible injury&raquo_space; severe/progressive&raquo_space;» IRREversible injury&raquo_space;> cell death via necrosis or apoptosis

Question 13

During the mechanism of cell injury, what does the cellular response depend on?

Answer 13

• Injury = type, duration and severity
• Cell = type, metabolic state, adaptability, and genetic makeup

Question 14

What are 8 cell characteristics of reversible cell injury?

Answer 14

• increased cell size
• chromatin clumping
• ER & mitochondria swelling
• small amorphous deposits in mitochondria
• membrane blebbing
• myelin figures
• pinched off ER segments (intracytoplasmic vacuoles)
• detachment of ER ribosomes

Question 15

What is hydropic change/vacuolar degeneration?

Answer 15

distended and pinched-off segments of the endoplasmic reticulum (ER)

Question 16

What is the fatty change in reversible cell injury?

Answer 16

appearance of lipid vacuoles in cytoplasm (common in organs involved in lipid metabolism)

Question 17

What are the 4 characteristics of IRReversible cell injury?

Answer 17

• breakdown of plasma membrane, organelles, and nucleus
• large amorphous deposits in mitochondria
• content leakage
• inflammation

Question 18

When does irreversible cell injury occur?

Answer 18

• inability to restore mitochondrial function = lose ability to store/make ATP
• altered structure + loss of function of plasma and intracellular membranes
• loss of structural integrity of DNA and chromatin

Question 19

What are the 6 mechanisms of cell injury?

Answer 19

• mitochondrial dysfunction
• oxidative stress
• membrane damage
• disturbance in calcium homeostasis
• ER stress
• DNA damage

Question 20

What are the 2 mechanisms of mitochondrial dysfunction?

Answer 20

• decreased ATP generation and depletion
• lack of ATP

Question 21

What is the mechanism of mitochondrial dysfunction via decreased ATP generation and depletion of ATP?

Answer 21

1) decreased ATP generation & ATP depletion&raquo_space;>
2) reduced activity of ATP-dependent plasma Na+ pumps&raquo_space;>
3) Na+ accumulates inside cell&raquo_space;>
4) osmotic gain of H2O&raquo_space;>
5) cell swells and dilates

Question 22

What is the mechanism of mitochondrial dysfunction via lack of ATP?

Answer 22

lack of ATP = increased anaerobic glycolysis&raquo_space;»> lactic acid build-up&raquo_space;» acidic inside cell&raquo_space;» decreased activity of cellular enzymes&raquo_space;» protein-synthesis apparatus disrupted&raquo_space;> Ca2+ influx = activates unwanted enzymes

Question 23

What is a reactive oxygen species (ROS)?

Answer 23

type of free radical = unstable chemical species w/ a single unpaired electron on outer shell

Question 24

How is a chain of free radicals produced?

Answer 24

when the “attacked” molecules converts into other types of free radicals

Question 25

What are the 2 types of oxidative stress mechanisms?

Answer 25

- physiological production - pathological production

Question 26

Mechanism of oxidative stress via physiological production?

Answer 26

redox reactions during cellular respiration

Question 27

5 mechanisms of oxidative stress via pathological production.

Answer 27

- phagocytic leukocytes when killing pathogens = release free radicals - ionizing radiation - chemical metabolism - metal accumulation - reperfusion

Question 28

What are the 3 things that oxidative stress can lead into?

Answer 28

- lipid peroxidation - protein modification = crosslinking - DNA mutation/breaks

Question 29

What is lipid perioxidation?

Answer 29

double-bonds in membranes = vulnerable >>>> membrane damage lipid-radical interation = peroxides = unstable and reactive = autocatalytic chain reaction

Question 30

How do free radicals induce protein modification?

Answer 30

radicals promote protein cross-linking enhanced degradation or loss of functional activity

Question 31

What are the 4 causes of membrane damage in cell injury?

Answer 31

- reactive oxygen species - decreased phospholipid biosynthesis - increased membrane degradation - cytoskeletal abnormalities

Question 32

How can reactive oxygen species cause membrane damage?

Answer 32

radical-lipid interaction = peroxide = autocatalytic chain reaction

Question 33

How can decreased phospholipid biosynthesis cause membrane damage in cell injury? What is it due to?

Answer 33

hypoxia/nutrient deprivation = decrease phospholipid biosynthesis = breakdown of membrane

Question 34

What causes the increase degradation of the membrane in cell injury?

Answer 34

increase phospholipase activity due to increase Ca2+ levels

Question 35

How do cytoskeletal abnormalities cause membrane damage?

Answer 35

disrupt anchors for plasma membrane = weakens integrity of membrane

Question 36

What can an excess of intracellular Ca2+ lead to?

Answer 36

activation of unwanted enzymatic activity

Question 37

What can result from an increased mitochondrial Ca2+?

Answer 37

increased permeability = release Cytochrome C into cytoplasm = not good

Question 38

What does endoplasmic reticulum stress cause?

Answer 38

misfolded proteins

Question 39

What happens when there is an abundance of misfolded proteins?

Answer 39

initiates/triggers apoptosis

Question 40

How does an accululation of misfolded proteins happen?

Answer 40

decreased degradation OR increased production

Question 41

How does protein misfolding cause disease?

Answer 41

creating deficiency of an essential protein or induces apoptosis

Question 42

How can DNA damage trigger apoptosis?

Answer 42

if too damage and no repairs worked

Question 43

What are the 2 types of cell death?

Answer 43

apoptosis and necrosis

Question 44

Why is necrosis considered an "accidental" cell death?

Answer 44

rapid/uncontrolled cell death

Question 45

What are 5 factors that necrosis is often due to?

Answer 45

- loss of O2/nutrients - ischemia - toxins - infections - trauma

Question 46

In necrosis, how is leakage of intracellular proteins beneficial?

Answer 46

allows for detection of tissue-specific necrosis

Question 47

How can hypoxia cause necrosis?

Answer 47

No O2 = anaerobic glycolysis = lactic acid build-up = acidic intracellular = decreased enzyme activity = ATP depletion = decreased ATP-Na+ pump activity = Na+ build-up inside cell = draws water inside cell = cell swells/dilates = bursts

Question 48

What are the 5 kinds of necrosis?

Answer 48

- coagulative - gangrenous - liquefactive - caseous - fat