L1 - A Kelly Flashcards

1
Q

Virchow proposed that ___ ____ is the basis of disease

A

Virchow proposed that cell injury is the basis of disease.

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2
Q

list some things which can inflict cell injury:

A

extremes of oxygen tension or pH; lack of ATP; exposure to toxins, drugs and chemical agents (xenobiotics); cold and heat; prolonged deprivation of vital nutrients;
trauma; and aging.

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3
Q

can acute and chronic inflammation affect host cells engatively?

A

yep

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4
Q

give some cellular responses to injury:

A
  • Hypertrophy – can adapt to stresses
  • Hyperplasia – increase in number of cells
  • Atrophy – reduction of complexity, and diminishing cell volume
    o Digestion of cytoplasm proteins
    o Autophagy – where organelles are encapsulated by intracytoplasmic membranes and digested by lysosomes
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5
Q

describe some reversible cell injury that may be seen:

A

Reversible injury may be seen as fatty deposits or cell swelling

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6
Q

what cause cell swelling?

A

Cell swelling is commonly caused by Na+/K+-ATPase (sodium/potassium pump) shut down leading to an influx of Na+ and hence H2O into the cell/mitochondria.

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7
Q

2 main methods by which cells die?

A

apoptosis

necrosis

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8
Q

describe apoptosis?

A
  • Requires cell to have control over its own metabolism
  • Common in tissue development and repair
  • Cell blebs and buds, and cytoplasm shrinks in volume.
  • Critical proteins cleaved by site specific protein caspases
  • Cell signals nearby phagocytes (macrophages) for immediate phagocytosis
  • Rarely induces inflammation
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9
Q

describe necrosis:

A
  • Loss of cell volume homeostasis – swelling
  • Rupture of membranes
  • Cellular contents can leak into blood stream
  • Will induce acute inflammation
  • Neutrophil activation may itself cause local cell injury.
  • Necrosis = poorly controlled process - tends to spread and involve sheets or groups of adjacent cells
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10
Q

the following lead to death by which mechanism?

  • loss of metabolic control
  • membrane damage
  • cytoskeletal damage
  • increased ROS
  • DNA damage
A
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11
Q

what are free radicals?

A

molecules with unpaired electrons – eg Nitric oxide
- Created by:

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12
Q

how are free radicals created?

A

o Ionising radiation
o Many xenobiotics

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13
Q

why are free radicals dangerous?

A

o Highly reactive
o Cause DNA strand scission
o Create more free radicals

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14
Q

are free radicals exclusively produced by pathogens?

A

nope - also used by neutrophils and macrophages to attack microorganisms – but they can damage host cells too

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15
Q

describe the process of Free radical production?

A

O2

O2*

H2O2

OH*

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16
Q

how are free radicals removed?

A

glutathione

Catalase

SOD

17
Q

describe hypoxia reperfusion injury?

A

Period after ischaema when blood flow is restored – ROS production increases and leads to tissue damage – destruction of endothelium of the blood vessels – recruits neutrophils = more damage, and thrombosis

18
Q

how can as a loss of cell energy metabolsim lead to cell death? (4)

A
  • Less ATP, reduced Na/K pump activity, Na+ accumulates in the cell, causing swelling
  • Increased lactic acid from increased glycolysis = decreased pH, decreased enzymatic activity
  • Influx of Ca2+ = increased activity of intracellular proteases, phospolipases, endonucleases and ATPases.
  • Ribosome detachment (or lack of attachement) and loss of protein synthesis
19
Q

_____ _____ are created by ionising radiation and also by many
xenobiotics

A

Free radicals

20
Q

free radicals are the normal by-products of reactions catalysed by many _____ ______

A

oxidase enzymes

21
Q

is the heat shock respone only to heat?

A

nope

also to other stresses

22
Q

Describe the heat shock response:

A
  • HSF form inactive complexes with HSP in cytosol
  • stress causes dissociation
  • HSF migrate to nucleus (also arent allowed to leave nucleus)
  • HSF trimerise
  • Supresses lots of generic gene transcription
  • Activate heat shock protein transcription
23
Q

what do heat shock proteins do?

A

– chaperone proteins which help refold partially denatured proteins.

24
Q

why dont heat shock proteins denature?

A
  • Unlike other proteins Hsps do not denature under conditions of stress as they have better hydrophobic packing, enhanced secondary protein structure, stronger hydrogen bonds and helix dipole stabilization.
25
Q

how are HSPs responsible for preconditioning?

A

where cells exposed to minor injury become resistant to more major stresses.

26
Q

HSP picture

A
27
Q

Describe the purpose of the unfolded protein response

A
  • ensures that the rate of protein synthesis does not exceed the cell’s capacity to complete the folding process.
  • ER protein conc can reach as high as 100mg/ml – if not folded and chaperones – can precipitate
28
Q

How does the unfolded protein response helpt to prevent protein precipitation in the ER

A

o increase synthesis of folding chaperones,
o enhances proteasomal protein degradation
o slows down protein translation
o usually reversible and is part of a process termed ‘host cell shut-down’.

29
Q

what is meant by ‘cell shut down’

A

Cell shut-down is a primitive reversible response to injury and is initiated within minutes. RNA and DNA synthesis is supressed and many enzyme-catalysed reactions are inhibited

30
Q

describe what activates the stress kinase pathway

A

(osmotic stress, oxidative stress, heat, UV, DNA cleavage)

31
Q

what does the stress kinase pathway ultimately modulate -

A

DNA transcription

32
Q

the stress kinase pathway activates _____ _____ _____ that reprogram transcription

A

heterodimeric transcription factors (e.g. AP1) that re- programme transcription

33
Q

important examples of stress kinase pathways

A

o Jun N-terminal Kinase (JNK)/stress-activated protein kinase pathway (SAPK) pathway
o P38 kinase pathway

34
Q

does the stress kinase pathway have a definitive outcome / answer?

A

nope - it just modulates discisions towards a stress response.

35
Q

stress kinase image

A
36
Q

Fat

A

Mamba

37
Q
A