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Year 2 > Cellular Injury > Flashcards

Cellular Injury Flashcards

1
Q

How do physicochemical agents cause cell destruction (2)

A
  1. Gross membrane disruption

2. Functional impairment

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2
Q

How does trauma and thermal injury caused by physicochemical agents cause cell destruction

A
  1. Denaturing proteins

2. Local vascular thrombosis -> Ischaemia or infarction

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3
Q

define thrombosis

A

Local clotting of blood in part of the circulatory system

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4
Q

How does freezing caused by physicochemical agents cause cell death

A
  1. Membranes are perforated by ice crystals
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5
Q

What are missile injuries

A

Combines effects of trauma and heat - energy is dissipated into tissues around the track

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6
Q

What are blast injuries

A

Result of SHEARING forces - where structures of differing density and mobility are moved with respect to one another

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7
Q

Give an example of blast injuries

A

Traumatic amputation

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8
Q

What wave causes thermal injury

A

Microwaves

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9
Q

What is the effect of low-energy laser light on cells

A

Produces tissue heating with coagulation

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10
Q

What is the effect of high-energy laser light on cells

A

Breaks intramolecular bonds by a photochemical reaction and vaporises tissue

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11
Q

Why do caustic agents cause rapid local cell death

A

Due to their EXTREME alkalinity and acidity

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12
Q

How do biological agents cause cell damage

A

By toxins and metabolic products that are secreted by bacteria

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13
Q

How do toxins cause cell death

A
  1. Affects membrane integrity or metabolism
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14
Q

What symptom is usually seen with toxin cell deaths

A

Acute Inflammation

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15
Q

How does acute inflammation induced by toxins affect neighbouring cells

A

Harms them

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16
Q

What are organisms secreting toxins called

A

Pyogenic

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17
Q

How do bacterial endotoxins function

A
  1. Induces apoptosis
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18
Q

Two factors that affect damage inflicted on tissues when toxins are involved

A
  1. Affect of toxins/ intracellular agents

2. Impact of host immune response to toxin

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19
Q

What effect on the metabolic pathway can cause cell injury

A

Blockage of the pathway

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20
Q

How does blockage of the metabolic pathway effect cellular respiration

A

Lack of Oxygen = Cell Death go many cells

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21
Q

How does cyanide effect the metabolic pathway

A

Cyanide ions bind to cytochrome oxidase and interrupt oxygen utilisation

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22
Q

How does blockage of metabolic pathway impact glucose levels

A

Deprives glucose levels which some cells are heavily dependant on

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23
Q

What cell depends on glucose the most

A

Cerebral neurones

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24
Q

How does a blockage in the metabolic pathway effect protein synthesis

A

Protein synthesis can be blocked at the translational level and there is a CONSTANT requirement to replenish enzymes and structural proteins

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25
Q

Name two antibiotics that would block the metabolic pathway for protein synthesis

A

Tetracycline

Streptomycin

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26
Q

How would growth factor or hormonal influence cause cell damage

A

A loss of them

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27
Q

How does a loss of growth factor or hormonal influence cause cell death

A

No intracellular cascade pathway -> cell undergoes apoptosis

Organs receiving hormones as messengers will shrink

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28
Q

How does ischaemia cause cell damage

A

Inadequate oxygen delivery
Mitochondrial production of ATP stops
Anaerobic Glycolysis = Acidosis due to lactate
Acidosis -> calcium influx

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29
Q

How does repercussion injury cause cell death

A
  1. After Ischaemia, blood supply may be restored

2. Large supply of O2 causes burst of mitochondrial activity and excessive release of free radicals of O2

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30
Q

How can free radicals be generated

A
  1. Deposition of energy

2. Oxidation-reduction reactions

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31
Q

How do free radicals cause cell damage

A

Damage to poly-unsaturated fatty acids or cell DNA

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32
Q

Why are poly-unsaturated fatty acids important

A

Important part of cell membrane

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33
Q

Why are poly-unsaturated fatty acids important

A

Important part of cell membrane

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34
Q

What happens to cells irreversibly damaged by free radicals

A

Deleted by apoptosis

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35
Q

Describe the four stages of clinicopathological events involving free radicals that lead up to cell death

A
  1. Toxicity of some poison
  2. Oxygen toxicity
  3. Tissue damage in inflammation
  4. Intracellular killing
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36
Q

What is the most important method by which cell death occurs

A

Failure of membrane integrity

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37
Q

What five ways can cause failure of membrane integrity

A
  1. Complement-mediated cytolysis
  2. Perforin-mediated cytolysis
  3. Specific blockage of ion channels
  4. Failure of membrane ion pumps
  5. Free radical attack
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38
Q

Define cytolysis

A

Disruption of cells

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39
Q

Define complement-mediated cytolysis

A

End products of complement cascade have cytolytic activity

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40
Q

What is perforin

A

Mediator of lymphocyte cytotoxicity

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41
Q

Define perforin-mediated cytolysis

A

Damage to cell membrane of target cells such as those infected by viruses

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42
Q

Why does specific blockage of ion channels cause lack of membrane integrity

A

Because they are needed for homeostasis

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43
Q

How does membrane pump failure effect membrane integrity

A

Interferes with mitochondrial oxidative phosphorylation or consuming ATP in chemical agent metabolism
Causes cell swelling

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44
Q

What is cell swelling due to pump failure called

A

Oncosis or hydronic change

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45
Q

What is cell swelling due to pump failure called

A

Oncosis or hydronic change

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46
Q

How do free radical attacks effect membrane integrity (2)

A
  1. Reactive oxygen species or phospholipase react with phospholipids causes lysosome permeability and release of its contents can cause further cell damage.
  2. Membrane proteins can be altered by cross-linking induced by free radicals
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47
Q

What sub-population of cells are most susceptible to DNA damage

A

Those that are constantly dividing

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48
Q

How can we tell if cell populations have DNA damage

A

Using a growth or metabolic stimulus

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49
Q

What is a neoplastic transformation

A

none-lethe DNA passed onto daughter cells causing abnormal growth characteristics

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50
Q

What can neoplastic transformations result in

A

Tumours

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51
Q

How is mitosis effected in cells that have severely damaged nuclei and what factors can cause this damage

A

It is blocked

Strand breaks
Base alterations
Cross-linking

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52
Q

How is DNA strand breakage usually caused

A

Radiation

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53
Q

How is the process of repair different if one strand was damaged compared to two strands damaged + why

A
  1. Single-damaged can be repaired (template present)

2. Double-damage cannot as multiple breaks can cause incorrect rejoining (template not present)

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54
Q

How does DNA strand cross-linking occur

A

When reactive oxygen species cause linkages between complementary strands + they can’t separate - this blocks replication

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55
Q

What are the two main sublethal cellular alteration types

A
  1. Hydropic change

2. Fatty Change

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56
Q

What is hydropic change

A

Results from disturbances of metabolism such as hypoxia or chemical poisoning

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57
Q

What is fatty change

A

Vacuolation of cells due to accumulation of lipid droplets as a result of disturbance to ribosomal function + uncoupling of lipid from protein metabolism

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58
Q

Can fatty change be reversed

A

Yes - moderate

No - Severe

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59
Q

What is autophagy

A

Cellular response to stress

1. Cell components are isolated into intracellular vacuoles and processed through to lysosomes

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60
Q

How can autophagy result in cell death

A

If stimulus is severe or metabolic pathway is switched to apoptosis

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61
Q

In what two ways does cell death happen

A

Apoptosis

Necrosis

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62
Q

What follows cell necrosis

A

Inflammation and repair

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63
Q

How is necrosis characterised

A

Bioenergetic failure

Loss of plasma membrane integrity

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64
Q

Why is an influx of calcium ions dangerous when ion channels are blocked

A

Because calcium uptake exceeds storage in mitochondria and disrupts inner membrane -> stopping production of ATP -> Contents leak into cytosol

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65
Q

How does DNA damage result in NAD and thus ATP depletion

A
  1. Initiates repair sequences
  2. Activates PARP enzyme
  3. Causes necrosis in cells proliferating due to lack of NAD and ATP (going into repair sequence instead)
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66
Q

How does falling ATP levels effect calcium ion uptake

A

Increases calcium conc. in cell cytosol
Activates calcium-dependant proteases
Decreased inner mitochondrial membrane permeability
Necrosis

67
Q

How does free radical damage to the ER effect calcium stores and what is the effect of this on the cell

A

Causes leakage into cytosol

Apoptosis (not necrosis)

68
Q

How does free radical damage to lysosomal membranes cause necrosis

A

Release of cathepsin (protease) which damages membrane

69
Q

How does tumour necrosis factor cause cell death

A

Binding to receptor -> excessive mitochondrial reactive oxygen species

70
Q

Pathways that result in necrosis have one separate process that takes place, what is this?

A

Inflammation caused by immunostimulation

Repair process

71
Q

Name the 6 types of necrosis

A 
Coagulative 
Colliquative
Gaseous
Gangrene
Fibrinoid
Fat Necrosis
72
Q

What is the most common type of necrosis

A

Coagulative

73
Q

Describe the process of coagulative necrosis

A
  1. Proteins coagulate to keep cell shape in tact.

2. Tissue texture goes from firm to soft due to digestion by macrophages

74
Q

Where in and why is coagulative necrosis dangerous in the heart

A

Myocardium following infarction can increase risk of ventricular rupture

75
Q

How can I tell if a cell is undergoing coagulative necrosis

A

Nuclei and cellular detail will be lost but you can still see a faint outline of the cell itself

76
Q

What effect follows coagulative necrosis

A

Inflammation

77
Q

Where does colliquative necrosis take place and why

A

Brain

Has a lack of support for the storm

78
Q

What happens during colliquative necrosis

A
  1. Necrotic neural tissue will totally liquidify
  2. Glial reaction around periphery
  3. Site of necrosis is marked by a cyst
79
Q

What happens during caseous necrosis

A

Dead tissue is structureless

80
Q

What disease can caseous necrosis be seen in

A

TB

81
Q

What happens during Gangrene

A

Necrosis with putrefaction of tissues

82
Q

Why do tissue effected by gangrene appear black

A

Due to deposition of iron sulphide from degraded haemoglobin

83
Q

What bacteria typically causes gangrene

A

Clostridia

84
Q

Where are clostridia typically found

A

Bowel

85
Q

What type of necrosis can lead to gangrene necrosis

A

Ischaemic

Intestinal

86
Q

Where is ‘wet’ gangrene found

A

Bowel (intestinal necrosis -> gangrene)

87
Q

Where is ‘dry’ gangrene found

A

In the toes due to ischaemic necrosis

88
Q

Name two types of gangrene that can be caused directly by bacteria

A

Gas Gangrene

Synergistic gangrene

89
Q

When does fibrinoid necrosis take place

A
  1. During malignant hypertension when high tension in arterioles causes necrosis of smooth muscle wall
  2. Allows seeping of plasma into media + deposition of fibrin
90
Q

How can I tell if fibrinoid necrosis has taken place on a slide

A

Vessel wall is bright red

91
Q

Two ways fat necrosis is caused

A
  1. Direct trauma to adipose tissue and extracellular liberation of fat
  2. Enzymatic lysis of fat due to release of lipases
92
Q

Describe the process of fat necrosis

A
  1. Trauma to adipose tissue causes release of intracellular fat
  2. Release -> inflammation
  3. Macrophages phagocytose fat
  4. Fibrosis
93
Q

Example of disease where fat necrosis takes place

A

Acute pancreatitis

94
Q

What are labile cells

A

Cells with a good capacity to regenerate

95
Q

Example of labile cells

A

Epithelium

96
Q

What are stable cell population cells

A

Divide at a slow rate and have capacity to replicate if necessary

97
Q

What are permanent cells

A

Cells with no regeneration abilities

98
Q

Examples of permanent cells

A

Nerve and striated muscle cells

99
Q

Where can stem cells be found

A

Basal layer of epidermis
Sebaceous glands
Bottom of crypts
Bone Marrow

100
Q

What can damage stem cell populations

A

Radiation

101
Q

What is complete restitution

A

Where labile cell population is completely restored

102
Q

Where can complete restitution take place

A

Epidermis

103
Q

Describe complete restitution in skin

A
  1. Epidermis lost over small area during abrasion
  2. Cells at margin of lesions and at sweat glands transected by braised site proliferate
  3. Spread until covered -> form confluent layer
  4. After layer is formed, stimulus is switched off (contact inhibition)
    ^ Scab
  5. Epidermis rebuilds from base upwards in process called healing
104
Q

What happens in neoplasia

A

Contact inhibition and process of healing is disrupted -> proliferation of cells into tumour

105
Q

When does granulation tissue develop

A

When specialised or complex tissue is destroyed

106
Q

Describe the process of granulation tissue development

A
  1. Repair takes place
  2. Capillary endothelium proliferate and grow into area to be repaired (start as buds -> channels)
  3. Channels loop around damaged area
  4. Fibroblasts stimulated to secrete collagen and divide
  5. Fibroblasts acquire muscle filaments and attach to adjacent cells (called myofibroblasts)
  6. Cause wound contraction and secrete collagen
107
Q

What does granulation tissue consist of

A

Loops of capillaries and myofibroblasts

108
Q

What is excessive granulation called

A

Proud flesh

109
Q

Why is wound contraction important

A

Reduce volume of tissue for repair by 80%

110
Q

What structure does collagen secreted by myofibroblasts produce

A

Scar

111
Q

What problems can wound contraction lead to

A

Stenosis (narrowing of blood vessels) and obstruction due to a stricture

112
Q

How does skin healed during an incised wound

A
  1. Little damage to tissues on either side of cut are brought close together
  2. Blood vessels cut are occluded by thrombosis
  3. Fibrin deposits and binds two sides.
  4. Coagulated blood on surfaces forms scab to keep wound clean.
  5. Capillaries proliferate to bridge gap
  6. Fibroblasts secrete collagen as they migrate into fibrin network
  7. Basal epidermal cells proliferate and spread over gap
  8. Wound is healed
113
Q

How does the size of the wound effect migration of fibroblasts

A

Migration would be less

114
Q

What happens to the excess of basal epidermal cells after the skin has healed

A

Resorbed

115
Q

How is healing different when tissues is lost or the sides of a wound are not close enough together

A
  1. Phagocytosis removes debris
  2. Granulation tissue to fill in defects and repairs specialised tissues
  3. Epithelial regeneration to cover the surface
116
Q

What factor effects the time-scale of healing by second intention

A

The amount of granulation tissue needed to cover the wound

117
Q

How are keloid nodules formed

A

Excessive fibroblast proliferation and collagen production after dermal injury

118
Q

What growth factor is produced by keratinocytes and macrophages

A

VEGF (vascular endothelial growth factor) - new blood vessels

119
Q

Role of PDGF (platelet - derived growth factor)

A

Facilitates local accumulation of macrophages, proliferation of fibroblasts and matrix production

120
Q

What growth factor controls myofibroblasts and collagen formation

A

TGF-beta

121
Q

Describe healing of mucosal erosions in the GI tract

A
  1. Epithelial cells adjacent to the defect proliferate to regenerate mucosa
122
Q

How long does it take for mucosal erosions to be fixed

A

Hours

123
Q

What is dangerous about mucosal erosions

A

Patients can lose a lot of blood before they heal

124
Q

Describe the process of healing during mucosal ulcerations

A
  1. Destroyed muscle can’t be regenerated
  2. Mucosa replaced from margins and spreads across base of ulcer
  3. Damaged blood vessels will have bled and surface is covered by fibrin
  4. Macrophages remove dead tissue
  5. Granulation tissue produced at ulcer base
  6. Capillaries and myofibroblasts proliferate
125
Q

What is the long-term consequence if the cause of an ulcer persists

A
  1. Ulcer becomes chronic and gastric wall can be destroyed
  2. Fibrous scar tissue replaces muscle and this will contract distorting stomach

Larger arteries in path of ulcer are at risk of rupture

126
Q

What is an endarteritis

A

Zone of inflammation around chronic ulcerations can obliterate the lumen

127
Q

What follows immediately from a bone fracture

A

Haemorrhage within the bone

128
Q

Where does haemorrhage in the bone come from

A

Ruptured blood vessels in the marrow cavity

129
Q

What is the benefit of a haematoma in bone fracture healing

A

It facilitates repair by providing a foundation for cell growth

130
Q

What are the stages of repair in fracture healing of bone

A
  1. Removal of necrosis tissue
  2. Organisation of haematoma
  3. Deposit bone as woven - forms a callus
  4. Woven bone replaced by lamellar bone
131
Q

What is a callus

A

Mass of bone with islands of cartilage

132
Q

What are the two layers of a callus (woven) bone

A
  1. Inner callus (medullary cavity)

2. Outer Callus (periosteum)

133
Q

What are five problems that can interfere with fracture healing

A
  1. Movement
  2. Interposed soft tissue
  3. Infection
  4. Misalignment
  5. Pre-existing bone disease
134
Q

How does movement delay bone fracture healing

A

Movement between two ends of bone causes excessive callus production - slows tissue union
Prevents bone formation
Collagen is laid down to give fibrous union

False Joint

135
Q

How does interposed soft tissue interfere with bone fracture healing

A

Found between broken ends and deals healing

136
Q

How does misalignment effect bone fracture healing

A

Prevent good functional result - leads to degenerative disease in joint

137
Q

In what type of fracture is infection most likely to have a negative impact on the healing process

A

Compound fractures

138
Q

Why is the liver able to heal effectively

A

High regenerative capacity of hepatocytes

139
Q

Other than hepatocytes, how can the liver regenerate (2)

A

From liver progenitor cells or bone marrow stem cells

140
Q

When can the liver not be healed

A

When hepatocytes AND hepatic architecture are severely destroyed

141
Q

What condition can failure to reconstruct hepatic architecture but regeneration of hepatocytes result in

A

Cirrhosis

142
Q

What other organ can be regenerated if the epithelium is destroyed but not when architecture is

A

Kidney

143
Q

What is the consequence of loss of tubular epithelium in the kidneys

A

Renal failure (this is the only exception where regeneration can’t happen) or damage to the glomerulus

144
Q

What is the issue with smooth muscle and cardiac muscle fibre damage during healing

A

They tend to be replaced by fibrous tissue

145
Q

In what condition can muscles be completely restored

A

If only the contractile proteins are lost

146
Q

What cell do voluntary muscle cells regenerate from

A

Satellite cells

147
Q

Define gliosis

A

Glial cells proliferate in response to injury to the CNS

148
Q

Can neurones regenerate in the CNS

A

No

149
Q

What two structures does peripheral nerve damage affect

A
  1. Axons

2. Schwann cells Oligodendrocyte

150
Q

When does wallerian degeneration take place

A

if there is a transection of the nerve

151
Q

What follows wallerian degeneration

A

Proliferation of Schwann cells

152
Q

Why do Schwann cells proliferate

A

For axonal regrowth

153
Q

Is full recovery of the CNS usual

A

No

154
Q

What can occur if the ends of the axons proliferate but the cut is uneven

A

Amputation neuroma

155
Q

What is the consequence of cell injury early in life

A

Prevention of normal growth and development of an organ.

156
Q

What can cause cell injury to a child

A

Infection

Mechanical Stress

157
Q

Why does ability to repair damaged tissues decrease as we get older

A
  1. Connective tissue becomes less elastic
  2. Renal function diminishes
  3. Bones weaken
  4. Cerebral neurones lost
158
Q

What immune response do nerves have a role in mediating

A

Inflammation

if denervated, inflammation may not work properly

159
Q

How are x-rays ionising

A
  1. High energy waves crash into atom causing it to become unstable and emit a photon.
160
Q

What particles cause ionisation

A

Alpha, beta and gamma particles

161
Q

how does UV light cause tumours

A

Damages DNA by inducing pyrimidine and strand linkages and is immunosuppressive

162
Q

What cells are found in skin tumours

A

Basal and squamous cell carcinomas

163
Q

What areas of the body are most sensitive to radiation

A

Gonads

Breast and bone marrow (half as sensitive)

Thyroid and bone

Year 2 (155 decks)

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