2. Cell Injury, Cell Death and Adaptations

Question 1

Reversible cell injury

Answer 1

Cell swelling, fatty change, plasma membrane blebbing and loss of microvilli, mitochondrial swelling, dilation of the ER, eosinophilia (resulting from decreased cytoplasmic RNA)

Question 2

Necrosis

Answer 2

Accidental cell death by increased cytoplasmic eosinophilia; nuclear shrinkage; fragmentation, and dissolution; breakdown of plasma membrane and organellar membranes; abundant myelin figures; leakage and enzymatic digestion of cellular contents

Question 3

Patterns necrotic tissue

Answer 3

Coagulative (everywhere), liquefactive + colliquative (brain), gangrenous, caseous (typical for tuberculosis), fat (pancreatitis), and fibrinoid (arterial wall),

Question 4

Apoptosis

Answer 4

regulated cell death to eliminate unwanted and irreparably damaged cells
enzymatic degradation of proteins and DNA
initiated by caspases and by rapid recognition and removal of dead cells by phagocytes

Question 5

Intrinsic initiation of apoptosis (Mitochondrial)

Answer 5

Triggered by loss of survival signals, DNA damage and accumulation of misfolded proteins (ER stress)
Associated with leakage of proapoptotic proteins from mitochondrial membrane
There they trigger caspase activation
Inhibited by anti-apoptotic members of Bcl family (induced by survival signals (including growth factors)

Question 6

Extrinsic initiation apoptosis (death receptor)

Answer 6

Elimination of self-reactive lymphocytes and damage by CTLs
Initiated by engagement of death receptors (members of TNF receptor family) by ligands on adjacent cells

Lethal signal from outside (FasL, TNF) triggers, thorugh receptor activation -> autocatalyc caspace activation
cytochrome c activates caspase 9
Phosphatidylserine flips to outside of cell membrane (signals other cells that cell can be taken up by other cells)

Question 7

Necroptosis and pyroptosis

Answer 7

Necroptosis: regulated by particular signaling pathways (necrosis and apoptosis features)
Pyroptosis: can lead to release of proinflammatory cytokines and may initiate apoptosis

Question 8

Autophagy

Answer 8

Adaptation to nutrient deprivation
Cells digest own organelles and recycle them to provide energy and substrates
Stress too severe: apoptosis

Question 9

Hypoxia and ischemia

Answer 9

ATP depletion and failure of many energy-dependent functions
First reversible injury, then necrosis

Question 10

Ischemia-reperfusion injury

Answer 10

Restoration of blood flow
Ischemic tissue exacerbates damage by increasing production of ROS and by inflammation

Question 11

Oxidative stress

Answer 11

accumulation of ROS
damage cellular lipids, proteins, and DNA
associated with many initiating causes

Question 12

Inflammation

Answer 12

associated with cell injury because actions of products of inflammatory leukocytes

Question 13

hypertrophy

Answer 13

increased cell and organ size
in response to increased workload
induced by growth factors produced in response to mechanical stress or other stimuli
occurs in tissues incapable of cell division

Question 14

hyperplasia

Answer 14

increased cell numbers
in response to hormones and other growth factors
occurs in tissues who are able to divide or contain abundant tissue stem cells

Question 15

atrophy

Answer 15

decreased cell and organ size
result of decreased nutrient supply or disuse
associated with decreased synthesis of cellular building blocks and increased breakdown of cellular organelles and autophagy
proteosomal degradation

Question 16

metaplasia

Answer 16

change in phenotype of differentiated cells
in response to chronic irritation (makes cells better able to withstand stress)
induced by altered differentiation pathway of tissue stem cells
may result in reduced functions or increased propensity for malignant transformation
replacement of one tissue by another tissue

Question 17

Depositions of lipids

Answer 17

Abnormal deposits of lipids (and more)
result of excessive uptake or defective transport or catabolism
Fatty change and cholesterol deposition

Question 18

fatty change

Answer 18

accumulation of free triglycerides in cells
results from excessive intake or defective transport (defects in synthesis of transport proteins)
manifestion of reversible cell injury

Question 19

cholesterol deposition

Answer 19

result of defective catabolism and excessive intake
seen in macrophages and smooth muscle cells of vessel walls in atherosclerosis

Question 20

deposition of proteins

Answer 20

reabsorbed proteins in kidney tubules; immunoglobulins in plasma cells

Question 21

deposition of glycogen

Answer 21

in macrophages of patients with defects in lysosomal enzymes that break down glycogen (glycogen storage disease)

Question 22

deposition of pigments

Answer 22

typically indigestible pigments (carbon, lipofuscin (breakdown of lipid peroxidation), or iron (overload (hemosiderosis)

Question 23

Pathologic calcification

Answer 23

Deposition of caclium
Distrophic calcification at site of cell injury and necrosis
Metastatic calcification in normal tissues, caused by hypercalcemia (usually consequence of parathyroid hormone excess)

Question 24

Combination of multiple progressive cellular alterations

Answer 24

accumulation of DNA damage and mutations
replicative senscence
defective protein homeostasis
aging

Question 25

Damaging agent

Answer 25

Etiology (ie radiation): missense mutation
Pathogenesis: replacement nucleotide, incorrect amino acid, malfunctioning protein
Adaptation: cell or organ reacts to minimize damage impact

Question 26

Cellular aging (telomere shortening)

Answer 26

DNA replicase cannot copy last piece of DNA
short telomere regions induce DNA damage response -> irreversible proliferation stop (cellular senscence)
Forced proliferation -> end-to-end joining of chromosomes -> chromosome breaks (aneuploidy, tumorigenesis)
telomerase can elongate telomeres (in stem cells and cancer cells)