Cell Injury, Cell Death and Cell Adaptation #1 (1/11/16)

Question 1

What is Etiology?

Answer 1

Origin of disease including underlying causes and modifiers (Why a disease occurs)

Question 2

What is Pathogenesis?

Answer 2

Development of disease, from molecular/cellular changes to functional and structural abnormalities (How a disease occurs)

Question 3

_____ is common to all forms of pathology.

Answer 3

Cellular injury

Question 4

What are 7 causes of cell injury?

Answer 4

Hypoxia (decreased oxygen levels)
Infectious agents (TB, Herpes, Candidiasis)
Physical injury
Chemicals/drugs (Gingival hyperplasia, Burns)
Immune response (Allergic responses)
Genetic abnormalities (Downs, Cancer)
Nutritional imbalance (Scurvy, Diabetes)

Question 5

T or F, Clinical signs and symptoms are usually several steps removed from the biochemical changes associated with cell injury?

Answer 5

True

Question 6

What are common targets for cellular injury? (4)

Answer 6

Cell membranes
Mitochondria
Cell Proteins
DNA

Question 7

What are the 6 Mechanisms of cell injury?

Answer 7

ATP depletion 
Generation of ROS
Loss of Ca++ homeostasis 
Altered membrane permeability 
Mitochondrial damage
DNA and Protein damage

Question 8

Describe the Hypoxia-Ischemia model….

Answer 8

1. So you get a thrombosis which blocks oxygen transport.
2. Oxidative phosphorylation decreases which decreases ATP production. (Increase in anaerobic glycolysis = decreased pH, lactic acid production, decreased glycogen stores and chromatin clumping)
3. This increases Na+ and Ca++ influx as we’ll as K+ Efflux.
4. Leads to increased H20 influx
5. Leads to cellular swelling, membrane blebs, loss of villi and ER swelling.

Question 9

The generation of ROS are associated with…..

Answer 9

• Inflammation
• Oxygen toxicity
• Chemical/drug metabolism
• Radiation
• Aging

Question 10

How do ROS cause damage?

Answer 10

Lipid Peroxidation
Protein Fragmentation
Single Strand Breaks in DNA

Question 11

Where are the major sites of single strand breaks by ROS?

Answer 11

Thymidine and Guanine

Question 12

How are ROS’s controlled?

Answer 12

Enzymes = Catalase, SOD and Glutathione peroxidase
Antioxidants = Vitamens E, A and C, Glutathione, cystine
Serum proteins that reduce/bind iron and copper needed to catalyze the formation of ROS.

Question 13

How does Ca++ induced Cell injury proceed?

Answer 13

Increased cytoplasmic Ionic Ca++ can lead to ATPase, phospholipases, protein disruption (Via protease) and DNA damage (via endonuclease)

Question 14

What determines the degree of cell injury?

Answer 14

• The Physiological state of the cell
• Intensity of the insult
• Duration of insult
• # of exposures to insult

Question 15

What are the 3 possibilities after cell injury?

Answer 15

1. May be reversible
2. May result in adaptation
3. Cell death (Necrosis or apoptosis)

Question 16

What are good examples of reversible cell injury?

Answer 16

Ischemia
Toxins
Infectious agents
Thermal injury

Question 17

T or F, there is no biochemical event that equates with cell death.

Answer 17

True, there is no line in the sand that indicates recovery vs death.

Question 18

What are the 4 types of Necrosis?

Answer 18

Coagulative = “Egg dropped into frying pan” = cells are frozen. Hypoxia-Ischemia.
Liquefactive = Liquid pus center (abscess)
Caseous = Granuloma forms around tissue with necrotic fluid in middle. (TB)
Enzymatic (Fat Necrosis) = Trauma to fatty tissue can release lipase that destroy fat.

Question 19

Which type of Necrosis is most common?

Answer 19

Coagulative

Question 20

What is Apoptosis important for (3 things)?

Answer 20

Normal cell turnover
Embryogenesis
Immune function

Question 21

What are conditions that involve excessive apoptosis?

Answer 21

AIDS
Ischemia
Neurodegenerative diseases
myelodysplasia 
Toxin induced liver injury

Question 22

What are diseases that inhibit apoptosis?

Answer 22

Cancer
Autoimmune diseases
Viral diseases

Question 23

Describe the morphology of Apoptosis…

Answer 23

1. Chromatin condensation
2. Progressive cell shrinkage
3. Plasma membrane blebbing
4. Apoptotic bodies
5. Phagocytosis = no inflammation

Question 24

What are the 2 mechanisms of Apoptosis?

Answer 24

1. Mitochondrial (intrinsic) pathway
2. Death receptor (extrinsic) pathway
   * END RESULT IS THE SAME WITH BOTH

Question 25

What is the stimuli for Necrosis vs Apoptosis?

Answer 25

Necrosis is always pathologic, where apoptosis can be physiological or pathological.

Question 26

______ occurs on a single cell basis where as ______ occurs at multiple cells.

Answer 26

Apoptosis = single cell 
Necrosis = multiple cells

Question 27

Is there inflammation with apoptosis?

Answer 27

No!

Question 28

What is atrophy?

Answer 28

Decrease in cell size and function 
From decreased:
- Nutrition
- Innervation
- Workload
- Blood supply

or Increased:
Age or local pressure

Question 29

What is Hypertrophy?

Answer 29

Increase in cell size and function with concurrent increase in organ size and/or function. 
From increased:
- Functional demand
- imbalance of nutrition
- hormonal stimulation (steroids)

Question 30

What is Hyperplasia?

Answer 30

Increase in Cell NUMBER with concurrent increase in organ size/function.

Question 31

What is Metaplasia?

Answer 31

Alteration in cell differentiation with concurrent alteration of tissue/organ function. *Squamous metaplasia of the bronchus due to smoking.
*Intestinal metaplasia of the esophagus

Question 32

What are some examples of intracellular accumulations?

Answer 32

Triglycerides (Steatosis) = Fatty liver
Cholesterol= Yellow skin papules (Xanthoma) or in vessels (atherosclerosis)
Protein = Mallory bodies and Alzheimer’s bodies
Carbs = Glycogen storage disease
Exogenous Carbon pigment = Anthracosis, Pneimoconicosis, amalgam tattoos, lipofuscin (Melanotic tattoo), Hemosiderin, Bilirubin.