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Flashcards in Inflammation Deck (53):
1

4 options for a cell under stress

Decreased ATP
Membrane damage
Increased intracellular a+2
Increased reactive oxygen species

2

Decreased ATP during stress leads to:

Loss of energy dependent cellular functions

3

Membrane damage during stress leads to:

Cell death
Enzymatic digestion of cellular components
Loss of cellular contents

4

Increased intracellular Ca+2 during stress leads to:

Protein damage and DNA breakdown

5

Increased reactive oxygen species during stress leads to:

Protein damage and DNA breakdown

6

ATP is produced by:

Oxidative phosphorylation or glycolysis

7

3 things that decrease as a result of ATP depletion

Repairing enzymes
ATP driven membrane ion pumps
Protein synthesis

8

4 things plasma membrane damage results in

Loss of cellular contents
Loss of osmotic balance
Influx of fluid and ions
Loss of proteins, enzymes, coenzymes and ribonucleic acids

9

Lysosomal membrane damage results in:

Autolysis by lysosomal enzyme leakage

10

Mitochondrial membrane damage results in:

Formation of nonselective high conductance channels in the mitochondrial membrane
This removes the transmembrane potential and cyt. C required for oxidative phosphorylation
Cyt. C leaks into cytosol and primes cells for apoptosis
Therefore leads to cell death and decreased ATP production

11

Mitochondrial permeability transition

The process of increasing nonselective high conductance channels in the membrane of the mitochondria allowing cytochrome C leakage

12

Calcium accumulation can activate:

ATPases
Phospholipases
Proteases
Endo and exonucleases

13

ATPases

Break down ATP and hasten depletion

14

Phospholipases

Break down lipid components of membranes causing leakage

15

Proteases

Break down membrane and cytoskeletal proteins causing structural damage and leakage

16

Endonucleases

Responsible for DNA and chromatin fragmentation

17

Exonucleases

Damage chromatin and RNAses

18

3 key reactive oxygen species

O2
H2O2
OH-

19

5 key free radicals

O2•
H2
O2
OH•
NO

20

Free radicals

Reactive molecules with single unpaired electron that release energy through reactions with adjacent molecules

21

Oxidative stress

Accumulation of free radicals which is toxic to cells
Generated by stressors sucks as irradiation, oxygen toxicity and drugs

22

3 ways that free radicals cause oxidative stress

Attack double bonds in UFAs leading to lipid peroxidation
Oxidise amino acid side chains leasing to enzyme damage
React with thymine causing DNA damange

23

Autocatalytic reaction

Positive feedback loop where free radicals react with close molecules thereby producing more free radicals which continue to react with adjacent molecules and so on

24

Heat shock factors

Signalling pathway activated by stress and injury
Transcription factors that induce expression of heat shock proteins which are molecular chaperones that help repair damaged proteins

25

5 key stress enzymes

p38 MAPK
p53
BMF
Bim
Bad

26

p38 MAPK

Initiates phosphorylation cascade

27

p53

Gatekeeper activated by DNA damage leading to cell suicide

28

BMF

Activated by actin cytoskeleton damage

29

Bim

Activated by microtubule damage

30

Bad

Activated by cell stress due to inadequate growth factor stimulation

31

Adaptation in response to mild injury or stress

Allows cells to continue to function despite changes
Hypertrophy, hyperplasia, atrophy, metaplasia

32

Necrosis process

1) Lysosomal membrane rupture
2) Autolysis
3) Cytosolic contents leak out of cell
4) Inflammation
5) Phagocytosis of debris

33

Dystrophic calcification

When necrotic debris is not promptly removed, calcium precipitation occurs which can harden and damage previously unaffected cells

34

Features of necrosis

Messy
Featureless cytoplasm
Faded or fragmented chromatin
Inflammation
Pathological
Affects surrounding cells

35

Apoptosis process

1) Cytochrome C leaks from mitochondrial membrane into cytoplasm
2) Chromatin cleaved and condenses
3) Organelles break off, immediately phagocytosed
4) Proteolytic cleavage of caspases removes inhibitory domains allowing executioner caspases to digest cellular proteins and activate digestive enzymes
5) Cell is digested from inside out without leakage, therefore no inflammation

36

Features of apoptosis

Controlled
Requires energy
Not pathological - normally due to recognised damage
No inflammation of surrounding area

37

Basic process of inflammation

1) Injured and necrotic cells release irritating pro-inflammatory substances
2) Macrophages and endothelial cells activated
3) Endothelial cells produce vasodilators
4) Blood flow increases, adhesion molecule expression increases
5) Neutrophil signalling and adhesion
6) Neutrophil migration, activation, survival, function and death
7) Inflammation reduction or chronic inflammation

38

Fibrinogen role in inflammation

Cleaved to fibrin which accumulates on epithelial surfaces and acts as a glue to seal damaged blood vessels and stabilise damaged tissues

39

Oedema

Accumulation of fluid in inflamed tissues due to exudation

40

Inflammation associated gene expression changes

Increased:
- Cell adhesion molecules
- Anti-apoptosis molecules
- Cytokines and chemokines
- Coagulation factors
- Pro-angiogenesis factors
Decreased:
- Cytoskeleton stabilisers

41

Hyperaemia

Increased blood flow

42

Exudation

Loss of fluid and protein

43

2 key cytokines that activate neutrophils after migration

IL-1 and TNF-aplha

44

Process of neutrophil migration

1) Rolling, slowing down by selectins
2) Integrin activation
- first stage of adhesion, binding of Sialyl-Lewis X modified glycoprotein to E and P selectins
3) Stable adhesion
- second stage of adhesion, integrins on neutrophil which used to have low affinity now bind to integrin ligand ICAM-1
4) Migration by squeezing through endothelial cells
5) Chemokine attraction of neutrophil to pathogen
6) Phagocytosis of pathogen
7) Cytokine release, attracting more leukocytes to inflammation site

45

2 key chemotactic factors causing chemotaxis of neutrophils after migration

IL-8
C5a

46

Neutrophils resist apoptosis in hypoxic damaged tissues by:

Changing expression of O2 dependent gene, increasing NFkB activity and promoting survival in target transcripts

47

5 local effects of inflammation

Redness
Swelling
Heat
Pain
Loss of function

48

4 systemic effects of inflammation

Fever
Leukocytosis
Acute Phase Proteins from liver
Increased glucocorticoid steroid hormones

49

4 examples of harmful acute inflammation

Rheumatoid arthritis (or any autoimmune condition)
Atherosclerosis
Allergy
Cytokine storm

50

As monocytes enter tissues they become:

Macrophages

51

After neutrophils, the 2 leukocytes that will next enter damaged tissues are:

Lymphocytes and macrophages

52

Granuloma

Specific pattern of chronic inflammation with necrotic core, microscopic aggregations of epithelioid macrophages and a collar of lymphocytes
Macrophages can fuse together into giant cells

53

3 paths after inflammation of a tissue

Resolution: tissue returns to normal
Repair: organisation into granulation tissue resulting in non-functional fibrous scar
Regeneration: tissue structure rebuilt, some function returns