Cell Adaptation and Injury

Question 1

Intrinsic/mitochondrial pathway of apoptosis initiation

Answer 1

• pro-apoptotic Bcl proteins dominate
• form channel in mitochondrial membrane
• release mito proteins like cytochrome C
• activate cysteine proteases/caspases

Question 2

Extrinsic pathway of apoptosis inititation

Answer 2

• Plasma membrane death receptors receive signals from outside to initiate apoptosis
• Fas ligand on T-cells bind Fas receptor->brings caspases together, cleave one another->cascade

Question 3

Necroptosis and Pyroptosis

Answer 3

morphologically like necrosis (loss of membrane integrity) but mechanistically like apoptosis (initiated by programmed signal transduction events)

Question 4

hyperplasia

Answer 4

• increased number of cells
• generally hormone and/or increased growth factors -> produce transcription factors -> more mitosis
• physiologic or pathologic
• if external stimulation stops, growth stops

Question 5

Hypertrophy

Answer 5

• increased size of cells due to increase in structural components
• growth factors and transcription factors-> increased production of cell structural components
• physiologic or pathologic

Question 6

atrophy

Answer 6

• decrease in cell size
• decreased demand/stimulation
• likely involve increased protein degradation: synthesis ratio
• physiologic or pathologic

Question 7

metaplasia

Answer 7

-one adult cell type is replaced by another
-usually from a more vulnerable->less vulnerable type
(eg columnar->squamous)
-reprogramming of stem cells

Question 8

steatosis

Answer 8

• intracellular accumulation of triglycerides (liver)

- round clear spaces in cytoplasm

Question 9

atherosclerosis

Answer 9

• accumulation of cholesterol in smooth muscle cells and macrophages within walls of large arteries
• intracellular-foamy appearance
• extracellular-clear shards

Question 10

amyloidosis

Answer 10

• abnormally folded proteins may deposit (usually extracellular)-may cause pressure atrophy of nearby cells
• glassy, pink, hyaline appearance
• composed of non-branching fibrils of B-pleated sheets
• Congo red stain-binds B-sheets well; apple green in polarized light

Question 11

Hyaline change

Answer 11

• glassy (homogenous) pink appearance
• often protein accumulation
• immunoglobulins in plasma cells-> Russell bodies

Question 12

glycogen accumulations

Answer 12

• may accumulate excessively in pts who have abnormalities in glycogen or glucose metabolism
• clear cytoplasmic (or occasionally nuclear in liver) vacuoles on H&E

Question 13

protein accumulations

Answer 13

• usually pink on H&E
• rounded, amorphous, fibrillar, or crystalline arrangement
• renal disease-eosinophilic droplets (protein) in proximal renal tubules

Question 14

carbon accumulations

Answer 14

• phagocytosed by macrophages in alveoli
• black lungs and lymph nodes
• anthracosis

Question 15

lipofuscin accumulations

Answer 15

• brown-yellow, finely granular cytoplasmic pigment
• incomplete breakdown of old subcellular components
• often heart and liver

Question 16

hemosiderin

Answer 16

golden yellow-brown granular/crystalline pigment-iron bound to ferritin protein

Question 17

irreversible injury

Answer 17

noxious stimulus of severe enough intensity or long enough duration will eventually injure cell to point where it can’t recover

Question 18

hypoxia

Answer 18

O2 deficiency

Question 19

ischemia

Answer 19

loss of blood supply (O2, glucose, ATP, etc); more rapid and severe damage

Question 20

physical causes of cell injury

Answer 20

• trauma
• temperature
• pressure
• radiation
• electric shock

Question 21

Chemical causes of cell injury

Answer 21

• may include substances that are required for cell fxn at physiological [ ], but toxic at high levels
• hypertonic glucose, salt, CO2
• poisons-arsenic, cyanide, mercury salts
• social stimuli-alcohol or tobacco
• therapeutic drugs

Question 22

Other causes of cell injury

Answer 22

infection
immunologic rxns and derangements
genetic derangements
nutritional deficiencies and imbalances

Question 23

targets of cell injury

Answer 23

• biochemical machinery of aerobic respiration
• integrity of cell membranes
• protein synthesis
• integrity of genetic apparatus

Question 24

Mechanisms of cell injury

Answer 24

• ATP depletion
• mitochondrial damage
• loss of Ca homeostasis
• defects in membrane permeability
• oxidative stress
• damage to DNA and proteins

Question 25

ATP depletion ->

Answer 25

• failure of plasma membrane Na/K ATPase->increase intracellular Na and decrease K->swelling
• switch to anaerobic metabolism->deplete glycogen stores, accumulate lactic acid-> decrease pH and activity of many enzymes
• failure of Ca iron pump->Ca influx
• damage to/degradation of protein synthetic apparatus-ribosomes detach from RER and polysomes-> monosomes -> decrease protein synthesis
• abnormal protein folding

Question 26

mitochondrial damage->

Answer 26

• mitochondrial permeability transition pore -high conductance channel in membrane->destroy potential
• cytochrome C, etc may leak->apoptosis

Question 27

Loss of Ca homeostasis->

Answer 27

Increased cytoplasmic Ca ->

• open mitochondrial permeability transition pore
• activation of numerous enzymes-phopholipases, proteases, endonucleases, ATPase
• directly activate caspase->apoptosis

Question 28

Principle free radicals

Answer 28

hydroxyl OH* -most reactive, most responsible for attacks on macromolecules
Superoxide anion O2-*
Hydrogen Peroxide H2O2
Peroxynitrite ONOO-

Question 29

Sources of free radicals

Answer 29

• byproduct of normal mito oxidative phosphorylation
• absorption of radiant energy
• leukocytes during inflammatory response
• metals (iron and copper)-fenton rxn
• nitric oxide-impt chemical mediator generated by endothelial cells

Question 30

removal of free radicals

Answer 30

antioxidants-Vit A, C, E, glutathione
transport proteins that bind reactive metals
enzymes-superoxide dismutase, catalase, glutathione peroxidase

Question 31

morphological changes of apoptosis

Answer 31

cell shrinkage, increased cytoplasmic density
nuclear pyknosis-small dark chromatin (apoptosis due to chromatin condensation and cleavage)
cytoplasmic blebs
apoptotic bodies which are rapidly cleared by phagocytosis

Question 32

morphological changes of necrosis

Answer 32

-denaturation of intracellular proteins and enzymatic digestion of the cell (takes time to develop)

Question 33

morphological changes of reversible injury

Answer 33

EM: plasma membrane blebbing, loss of microvilli, mitochondrial swelling, ER dilation
LM: cellular swelling, clear cytoplasmic vacuoles, fatty change

Question 34

morphological changes of irreversible injury

Answer 34

EM: membrane discontinuity, marked mitochondrial swelling, myelin figures (whorled phospholipid masses)
LM: cytoplasmic eosinophilia, calcification of FAs, nuclear changes- karyolysis (fading chromatin), pyknosis (small dark chromatin), karyorrhexis (chromatin fragmentation), loss of nucleus

Question 35

coagulative necrosis

Answer 35

architecture of tissue is preserved for at least a few days (often ischemia)

Question 36

liquefactive necrosis

Answer 36

dead cells completely digested, leaving only viscous liquid (bacterial and fungal infections, hypoxia in CNS)

Question 37

caseous necrosis

Answer 37

“cheesy” granular material (TB infection)

Question 38

fat necrosis

Answer 38

areas of fat destruction; FA products and calcium; chalky white areas (pancreatitis and pancreatic lipase)

Question 39

dystrophic calcification

Answer 39

• deposit Ca salts in dying tissues
• occurs despite normal serum Ca levels
• membrane damage initiates Ca concentration in cellular vesicles
• H&E stain deeply basophilic (blue/purple)
• intra or extra cellular
• all 4 types of necrosis, atherosclerosis, damaged/aging heart valves

Question 40

metastatic calcification

Answer 40

increased serum Ca (often in otherwise normal tissues)