Growth Adaptations, Cell Injury and Cell Death

Question 1

describe the mechanisms of cell injury and how it affects the organelles

Answer 1

Question 2

describe why hypoxia causes cellular injury

Answer 2

• low O2 delivery to tissue; important cause of cellular injury
  
  • O2 is the final electron acceptor in the ETC of oxidative phosphorylation
  • decreased O2 impairs oxidative phosphorylation, resulting in decreased ATP production
  • lack of ATP (essential energy source) leads to cellular injury

Question 3

low ___ disrupts key cellular functions, including: ____

Answer 3

low ATP disrupts key cellular functions, including:

• Na/K pump, resulting in sodium and water buildup in the cell
• Ca2+ pump, resulting in Ca2+ buildup in the cytosol of the cell
• switch to anaerobic glycolysis
  
  • lactic acid buildup results in low pH which denatures proteins and precipitates DNA

Question 4

the initial phase of injury is ____; the hallmark of ____ injury is ____

explain this concept

Answer 4

the initial phase of injury is reversible; the hallmark of reversible injury is cellular swelling

• cytosol swelling results in loss of microvilli and membrane blebbing
• swelling of the rER results in dissociation of ribosomes and decreased protein synthesis
• blebs, myelin figures (cell memb.), mt swelling

Question 5

the hallmark of irreversible injury is _____

explain examples of this in the cell

Answer 5

the hallmark of irreversible injury is membrane damage

• plasma membrane damage results in:
  
  • cytosolic enzymes leaking into the serum (cardiac troponin)
  • additional Ca2+ entering into the cell
• mitochondrial membrane damage results in:
  
  • loss of the ETC (inner mt membrane)
  • cytochrome c leaking into cytosol (activates apoptosis)
• lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which, in turn, are activated by the high intracellular Ca2+

Question 6

describe what is seen in the image

Answer 6

Question 7

describe what is seen in the image

Answer 7

Question 8

describe injury to the nucleus

Answer 8

Question 9

describe injury to the lysosomes

Answer 9

Question 10

describe injury to mitochondria

Answer 10

Question 11

list reversible ischemic injury events

Answer 11

• impaired aerobic respiration (mt)
• decreased ATP (energy)
• anaerobic glycolysis
• glycogen depletion
• lactic acidosis and nuclear chromatin clumping

Question 12

list the sequence of events in reversible injury

Answer 12

Question 13

the critical point of cellular injury is the inability of ___ to recover

Answer 13

the critical point of cellular injury is the inability of mitochondria to recover

Question 14

list the sequence of events for an irreversible injury

Answer 14

Question 15

describe injury by free radicals and explain what most free radicals do

Answer 15

most affect cell membranes producing energy loss

• the most common = activated oxygen radicals (aging, chemical, x-rays, infxns, inflammation, tumors, etc.)
• free radicals affect cell membranes by lipid peroxidation and affect nucleic acids with mutations
• protective mechanisms (antioxidants) = catalase, glutathione

Question 16

give an example of direct effect of chemicals on cells

Answer 16

• direct = Hg (mercury) binds to proteins and cell membranes

Question 17

describe coagulative necrosis

Answer 17

most common type of necrosis

• necrotic tissue that remains firm
• cell shape and organ structure are preserved by coagulation of cellular proteins
• nucleus disappears
  
  • acidophilic mass (since nucleus no longer stains basophilic)
• characteristic of ischemic infarction of any organ except brain

Question 18

describe liquefactive necrosis and name the 3 situations it is seen in

Answer 18

• necrotic tissue becomes liquified
• enzymatic lysis by hydrolytic enzymes of cells and proteins results in liquefaction
• characteristic of:
  
  • brain infarction
  • abscess (bacterial infxns)
  • pancreatitis

Question 19

describe fat necrosis

Answer 19

• necrotic adipose tissue with chalky-white appearance due to deposition of calcium
• in fat, release of lipases from dead pancreatic cells –> FFA + Ca2+ = saponification
  
  • example of dystrophic calcification

Question 20

describe gangrenous necrosis

Answer 20

• coagulative necrosis that resembles mummified tissue (dry gangrene)
• characteristic of ischemia of lower limb and GI tract
• if superimposed infection occurs, then liquefactive necrosis ensues (wet gangrene)

Question 21

describe caseous necrosis

Answer 21

• soft, friable necrotic tissue with “cottage cheese-like” appearance
• eosinophilic
• combination of coagulative + liquefactive necrosis
• characteristic of granulomatous inflammation due to TB or fungal infection

Question 22

describe fibrinoid necrosis

Answer 22

• necrotic damage to blood vessel wall
• leaking of proteins into vessel wall results in bright pink staining
• characteristic of malignant hypertension or vasculitis

Question 23

describe intracellular accumulations

Answer 23

• fatty change = accumulation of lipids
• accumulation of proteins = Ig (Russell bodies)
• accumulation of glycogen = storage disorders, diabetes
• mixtures of lipids and carbohydrates = mucopolysaccharides

Question 24

describe how free radicals cause damage

Answer 24

• peroxidation of lipids
• oxidation of DNA and proteins
  
  • DNA damage is implicated in aging and oncogenesis

Question 25

name the enzymes that eliminate free radicals

Answer 25

• superoxide dismutase (in mt) + superoxide (O2-) = H2O
• glutathione peroxidase (in mt): 2GSH + free radical = GS-SG and H2O
• catalase (in peroxisomes): H2O2 –> O2 and H2O

Question 26

describe chemical injury due to carbon tetrachloride (CCl₄)

Answer 26

• converted to CCl₃ free radical by P450 system of hepatocytes
• results in cell injury with swelling of rER; consequently, ribosomes detach, impairing protein synthesis
• decreased apolipoproteins cause accumulation of lipid in cells (ER) because apolipoproteins are necessary for triglycerides to leave the cell
  
  • lead to fatty change in the liver

Question 27

describe what is seen in this image

Answer 27

fatty liver

Question 28

describe viral injury

Answer 28