Cell degeneration and death 1

Question 1

Pathogenesis

Answer 1

how a disease state develops

Question 2

Degeneration

Answer 2

cell injury that falls short of cell death, usually reversible

Question 3

programmed cell death

Answer 3

regulated, controlled cell death

Question 4

apoptosis

Answer 4

a specific form of PCD, may be pathological or physiological

Question 5

Necrosis

Answer 5

pathological cell death in the tissues of a living animal due to lethal cell injury

Question 6

Autolysis

Answer 6

cell death that occurs after the animal dies

Question 7

Putrefaction

Answer 7

bacterial lysis and fermentation of tissue in a dead animal

Question 8

Cell injury concepts

Answer 8

normal cells –>injurious stimulus–>injured cell–>necrosis/apoptosis

normal cell–>adapted cell–>adaptive capacity exceeded–>injured cell–> necrosis/apoptosis

Question 9

Cellular responses to sublethal injury

Answer 9

-metabolically active cells are susceptible to injury
-constant import, export, and synthesis of molecuels
-sublethal injury may shift metabolic pathways such that these molecules accumulate in large amounts
-intracellular inclusions
-

Question 10

Are all intracellular inclusions the product of cell damage?

Answer 10

no, many accumulate in cells carrying out normal function

hepatocytes, macrophages, aging cells

Question 11

Mechanisms of accumulation

Answer 11

• increased biosynthesis
• decreased excretion/secretion
• diminished intracellular consumption
• reduced metabolism/decreased transformation of a precursor molecule into its product
• increased uptake from the extracellular compartment
• inability to enzymatically degrade endogenous or exogenous substances

Question 12

Categories of intracellular material

Answer 12

• normal cellular molecules accumulated to excess (h20,lipids,glycogen)
• foreign substances
• pigments
• metal ions (Cu,Fe) that accumulate to excess or are not excreted properly
• Ca in necrotic cells
• microbial (bacterial, viral, protistan) structures

Question 13

Physiological causes for hepatic lipidosis

Answer 13

alcoholism
fatty diet
changes in metabolism
starvation

Question 14

Characteristics of fatty liver

Answer 14

liver is enlarged, friable, rounded edges, more yellow, greasy

Question 15

Cell death may be? How?

Answer 15

physiological or pathological

• physiologic- skin cells die as they mature
• pathological-due to disease/cell injury

Question 16

Causes of cell injury and death

Answer 16

• chaotropic chemical and physical insults
• lytic cell insults- lysis (viral infections), pores (complement proteins, cytoxic T-cell)
• hypoxia
• impaired cell membrane function or integrity
• damage to nucleic acids
• ligand-receptor mediated signals

Question 17

Apoptosis important for?

Answer 17

involution
atrophy
t-cell removal
embryogenesis
glucocorticoids
tumours
injurious stimuli that are too weak to cause necrosis

Question 18

Disorder associated with disregulated apoptosis include?

Answer 18

increased apoptosis causing abnormally high reates of cell death- ex virus associated with lymphocyte depletion (AIDS)
Inhibited apoptosis and increased cell survival
-tumours- related to p53 mutations/hormone dependence
-autoimmune disorders- autoreactive lymphocytes not removed

Question 19

Describe the process of apoptosis

Answer 19

Signalling
-transmembrane or intracellular; numerous signals
Control/integration
-biochemical integration of pro- and anti-apoptotic factors in the cell dictate outcome of signal
Execution phase
-death program mediated mainly by caspasese; cysteine-ASPartic residues, bioamplification system
Phagocytosis
-membrane flipping-cell displays signals on the surface that say eat me- get phagocytosed

Question 20

Is there inflammation involved in apoptosis?

Answer 20

NO

Question 21

Four main mechanisms of cell injury

Answer 21

depletion of ATP
damage to nucleic acids, especially DNA
interference with protein synthesis
injury to cell membranes

Question 22

How does necrosis work?

Answer 22

lethally injured cells accumulate large amounts of intracellular Ca
-activation of phospholipases–>progressive cell lysis of all membranes–> activate proteases–>dissolve cytoskeleton–>inactivate enzymes–>denature proteins

Question 23

What is the overall effects of marked increase of intracellular Ca in necrotic cells

Answer 23

it results in inappropriate activation of proteases, phospolipases, ATPases and endonucleases

Question 24

Ischemia

Answer 24

lack of blood flow

• castration of cattle with elastic bands
• thrombosis- blood clots- heart attack/stroke

Question 25

Dystrophic calcification

Answer 25

necrotic tissue may also calcify

Question 26

Microscopic hallmarks of necrosis

Answer 26

hypereosinophilia and homogeneity of cytoplasm

nuclear changes- pyknosis, karyorrhexis, karyloysis

Question 27

Pyknosis

Answer 27

most commonly seen nuclear change in necrosis- probably due to tight coiling of DNA at low cellular pH

Question 28

Karyorrhexis

Answer 28

fragmentation of the nucleus seen frequently when necrosis is caused by infectious agents

Question 29

Karyolysis

Answer 29

dissolution or fading away of the nucleus due to dissolution of DNA by DNAases released at low pH

Question 30

Comparison of necrosis and apoptosis

Answer 30

Necrosis Apoptosis

1. swells 1.shrinks
2. coagulation/liquefies 2. cytoplasm packed into blebs
3. memb. frag 3. memb intact
4. disorganized 4.organized
5. ATP depleted 5. ATP required
6. contents leak 6. no leaks
7. inflammation 7. no inflammation
8. messy 8.clean
9. inflammation 9. NO inflammation

Question 31

Describe how necrosis stimulates inflammation

Answer 31

Leukocytes recruited to necrotic tissue

Leukocytes surround the regions of necrosis and begin to infiltrate the necrotic tissue

Question 32

Macroscopic appearance of necrotic tissue

Answer 32

coagulation necrosis
-retains architectural resemblance to normal
-pale, swollen, friable
liquefactive necrosis
-architecture lost
-pale,liquid but texture may vary
caseation necrosis 
-architecture lost
-dry or cheese-like consistency, friable