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ESA 2- Mechanisms of Disease > Cellular Adaptations > Flashcards

Flashcards in Cellular Adaptations Deck (319):
1

What does the size of cell populations in adults depend?

The rate of cell proliferation, cell differentiation and cell death by apoptosis

2

What are increased cell numbers seen with?

Increased cell proliferation or decreased cell death

3

What may cell proliferation occur as the result of?

Physiological or pathological conditions

4

Give an example of where excessive physiological stimulation can become pathological

Prostatic hyperplasia

5

What do proto-oncogenes do?

Regulate normal cell proliferation

6

How do cells in a multicellular organisms communicate?

Through chemical signals

7

How is cell proliferation largely controlled?

Largely by signals (soluble or contact dependant) from the microenvironment which either stimulate or inhibit cell proliferation

8

What are the potential final outcomes of signalling biochemistry?

Divide
Differentiate 
Survive
Die

9

How do cells divide?

They enter the cell cycle

10

What happens when cells differentiate?

They take on a specialised form and function

11

How do cells die when signalled?

They undergo apoptosis

12

What are the types of cell signalling?

Autocrine 
Paracrine 
Endocrine

13

What is autocrine signalling?

Cells respond to the signalling molecules that they themselves produce

14

What is intracrine signalling?

A type of autocrine signalling whereby the cell synthesises a factor which has an effect by binding to intracellular receptors within the cell. 
The factor is therefore not secreted by the cell

15

What is paracrine signalling?

A cell produced the signalling molecule, which acts of adjacent cells

16

Where are the effector cells in paracrine signalling?

Close to the secreting cell

17

Are the cells affecting by paracrine signalling the same as the one secreting?

No, they are often of a different type

18

What is endocrine signalling?

Hormones are synthesised by cells in an endocrine organ, and then conveyed in the blood stream to target cells to effect physiological activity

19

What happens when a signalling molecule binds to a receptor?

It causes a series of events, which results in modulation of gene expression

20

Where are the receptors to signalling molecules located?

Usually in the cell membrane, but can also be in the cytoplasm or nucleus

21

Give an example of a type of receptor located in the nucleus?

Steroid hormone receptors

22

What can cell to cell signalling be via?

Local mediators 
Direct cell-cell or cell-stroma contract
Hormones

23

What is particularly important amongst local mediators for cell proliferations?

Growth factors

24

What are growth factors?

Polypeptides that act on specific cell surface receptors

25

What codes for growth factors?

Proto-oncogenes

26

How do growth factors differ from hormones?

Hormones from endocrine organs travel via the blood stream to reach their target cells, whereas growth factors act only over a short distance, or on the secreting cell itself

27

Do growth factors act on many cell types, or restricted targets?

There are many different types of growth factors, some which act on many cell types and some on restricted targets

28

What do growth factors do?

Stimulate cell proliferation or inhibition 
May also affect cell locomotion, contractility, differentiation viability, activation and angiogenesis

29

How do growth factors exert their effects?

They bind to specific receptors and stimulate transcription of genes that regulate the entry of the cell into the cell cycle and the cell’s passage through it

30

Give 4 examples of growth factors

Epidermal growth factor 
Vascular endothelial growth factor
Platelet-derived growth factor 
Granulocyte colony-stimulating factor

31

What does epidermal growth factor (EGF) do?

Mitogenic for epithelial cells, hepatocytes and fibroblasts.

32

What produces EGF?

Keratinocytes, macrophages and inflammatory cells

33

What does EGF bind to?

Epidermal growth factor receptor (EGFR)

34

What does vascular endothelial growth factor (VEGF) do?

It is a potent inducer of blood vessel development (vasculogenesis), and has a role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing

35

Where is platelet-derived growth factor (PDGF) stored?

In platelet α granules

36

When is PDGF released?

On platelet activation

37

Other than platelets, what produced PDGF?

Macrophages, endothelial cells, smooth muscle cells and tumour cells

38

What doe PDGF do?

Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes

39

What does granulocyte colony-stimualting factor (G-CSF) do?

Stimulates the bone marrow to produce granulocytes, particularly neutrophils, and release them into the blood

40

What is G-CSF used as?

A treatment to stimulate poorly functioning bone marrow, e.g. during chemotherapy

41

What happens when a cell receives instruction to divide?

The cell enters the cell cycle

42

What is the sequence of the cell cycle?

G1 →  S →  G2 →  M

43

What happens after cell cycle completion?

The cell either re-starts to process from G1, or exists (G0) until further growth signals occur

44

What can happen to cells in G0?

They can undergo terminal differentiation

45

What is the result if cells undergo terminal differentiation?

There is a permanent exit from the cell cycle

46

How does increased growth of tissue occur?

Either by shortening the cell cycle, or by conversion of quiescent cells to proliferating cells by making them enter the cell cycle

47

What can be seen of the cell cycle under the light microscope?

Only M (mitosis) phase is distinctive

48

What does the M phase of the cell cycle consist of?

Mitosis and cytokinesis

49

What is mitosis?

Cellular division

50

What is cytokinesis?

Cell division to yield two daughter cells

51

What is the part of cell cycle that isn’t M called?

Interphase

52

What does interphase encompasses?

G1, S, and G2

53

What is G1?

Gap 1- pre synthetic, where the cell grows

54

What is S?

DNA synthesis

55

What is G2?

Gap 2, premitotic where the cell prepares to divide

56

Cumulatively, what does interphase include?

DNA replication and protein synthesis for growth in cell size

57

What is cell cycle progression controlled by?

Key ‘checkpoints’ which sense damage to DNA and ensure cells with damaged DNA do not replicate

58

What is the most critical cell cycle checkpoint?

Restriction (R) point

59

When is R?

Towards the end of G1

60

What happens to cells that pass the R checkpoint?

The majority of them will complete the full cell cycle

61

What happens if R checkpoint activation occurs?

The p53 protein suspends the cell cycle and triggers DNA repair mechanisms, or, if the DNA cannot be repaired, apoptosis.

62

Where are the other cell cycle checkpoints?

At the G1/S transition, and G2/M transition

63

What is checked for at the G1/S checkpoint?

DNA damage before DNA replication

64

What is checked for at the G2/M checkpoint?

DNA damage after DNA replication

65

What are defective cell cycle checkpoints a major cause for?

Genetic instability in cancer cells

66

What is progression through the cell cycle tightly regulated by?

Proteins called cyclins and associated enzymes called cyclin-dependent kinases (CDKs)

67

Which stage of the cell cycle is particularly tightly regulated?

The G1/S transition

68

How do CDKs become active?

By binding to and complexing with cyclins

69

How do activated CDKs drive the cell cycle?

By phosphorylating proteins that are critical for progression of the cell to the next stage of the cell cycle

70

What is the activity of cyclin-CDK complexes tightly regulated by?

CDK inhibitors

71

How do growth factors work, with regard to CDKs?

Some by stimulating the production of cyclins 
Some by shutting off production of CDK inhibitors

72

How are cells classified based on their ability to multiply?

Labile 
Stable
Permanet

73

What are labile cells?

Cells that continue to multiply through their life

74

What are stable cells?

Cells that can multiply in a regenerative burst, but are usually quiescent

75

What are permanent cells?

Cells that cannot proliferate

76

How has the classification of cells depending on how they divide been modified?

Following our understanding that many terminally differentiated cells can’t divide, and following the discovery that cells in a tissue are very often replaced by cells derived from stem cels and not mature differentiated cells

77

Are stem cells present in adult tissues?

Yes, many of them

78

What are stem cells?

Cells with prolonged proliferative activity which show asymmetric replication

79

What happens in asymmetric replication?

One of the daughter cells remains as a stem cell while the other differentiated into a mature, non-dividing cell

80

How are embryonic stem cells different to normal adult stem cells?

In that they are pluripotent and can give rise to any of the tissues in the human body. Adult stem cells can usually only give rise to one type of adult cell- their lineage is specific

81

How has the classification of cells by their ability to divide developed?

We now consider the classification in relation to tissues (a group of similar specialised cells with a specific function)

82

What can cell populations be classified as?

Permanent cell populations 
Labile cell populations 
Stable cell populations

83

What has happened in permanent cell populations?

The terminally differentiated cells within some tissues have left the cell cycle and cannot replicate

84

Give 3 examples of permanent cell populations?

Cardiac muscle 
Skeletal muscle 
Neural tissue

85

Can stem cells be present within permanent cell populations?

Yes, but they cannot mount an effective proliferative response against significant cell loss

86

What happens if neurones are destroyed?

The tissue space is filled by glial cells

87

How does skeletal muscle have a very limited regenerative capacity?

Through stem cells attached to the endomysial sheath

88

How does damage to the heart heal?

With a scar

89

Why does damage to the heart heal with a scar?

Because no stem cells are present in the heart

90

Give two examples of labile cell populations

Bone marrow
Epithelium

91

What do labile cell populations such as in bone marrow and epithelium consist of?

Mature differentiated cells that cannot replicate

92

Why is tissue such as bone marrow and epithelium considered proliferative?

As the cells in them are short lived, and are continually being replaced by cells derived from stem cells

93

What can stable cell populations be said to be?

An intermediate between permanent and labile tissues

94

Give two examples of stable cell populations

Liver
Kidney

95

What cells are involved in proliferation in stable cell populations?

Mature cells as well as stem cells

96

Give 5 examples of cells that are usually non-replicating, but can be induced to enter to cell cycle and replicate if necessary

Liver hepatocytes 
Bone osteoblasts
Fibroblasts
Smooth muscle cells
Vascular endothelial cells

97

What is required to induce a usually non-replicating cell to enter the cell cycle?

A large number of genes

98

What genes are required to induce a usually non-replicating cell to enter the cell cycle?

Proto-oncognes
Genes required for ribosome synthesis and protein translation

99

Are stem cells present in stable cell populations?

Yes

100

What state are the stem cells in stable cell populations in?

Usually quiescent, or proliferate very slowly, however they can proliferate persistently when required

101

What is the regenerative capacity of bone?

Very good

102

What is the regenerative capacity of tendons?

Poor

103

Why do tendons heal very slowly?

As they have few cells and few blood vessels

104

What is the result of tendons healing very slowly?

Secondary rupture at a site of previous injury is not uncommon

105

What is the regenerative capacity of articular cartilage?

Poor

106

What is the regenerative capacity of adipocytes?

Nil

107

How are new fat cells formed?

By undifferentiated but committed cells that lie among the adipocytes

108

What is the regenerative capacity of epithelia?

Very good

109

What exceptions are there to epithelia having a very good regenerative capacity?

Lens of the eye 
Renal podocytes

110

Where will surface epithelia regenerate?

Over denuded areas

111

What is the regenerative capacity of the liver?

Very good

112

How is the regeneration capacity of the liver shown in transplant patient?

Transplanted livers adjust their size to the size of the recipient

113

What is the regenerative capacity of mesothelia?

Good

114

What is the regenerative capacity of melanocytes?

They tend to regenerate too little or too much

115

What colour are scars in pigmented skin?

Usually pale

116

What is the regenerative capacity of smooth muscle?

Very good

117

What is the regenerative capacity of striated muscle?

Limited

118

What is the regenerative capacity of peripheral nerves?

Regenerate in a predictable way

119

How quickly do sprouting axons grow?

1-3mm/day

120

What happens if the gap regenerating axons have to cross is too wide?

They form a disordered tangle, which can result in a painful amputation neuroma

121

What is the regenerative capacity of neurone?

None (in humans)

122

When do neurones cease to multiply?

Before birth

123

How can lost neurones be replaced?

They can’t

124

How do people with hemiplegia secondary to strokes recover?

Because of the ability of the CNS to establish alternative pathways

125

What is the ability of the CNS to establish alternative pathways called?

Plasticity

126

How can cells respond to challenges that are not severe enough to cause injury?

By adaptations that are not truly pathologic, although they may open the door to disease

127

What is cell adaptation?

The state between a normal unstressed cell, and an overstressed cell

128

Is cell adaptation reversible?

Normally

129

What are the important types of cell adaptation?

Regeneration 
Hyperplasia 
Hypertrophy 
Atrophy 
Metaplasia

130

What is regeneration?

The replacement of cell losses by identical cells in order to maintain the size of a tissue or organ

131

Give an example of when is regeneration a normal process

Replacement of red and white blood cells by the bone marrow

132

When can regeneration occur after injury by a harmful agent?

If the harmful agent is removed, and there is limited tissue damage

133

When is resolution of injury not possible?

If the harmful agent persists 
If there is extensive tissue damage
If the damage occurs to a permanent tissue

134

What happens when regeneration is not possible?

The tissue will heal with a scar

135

Give two examples of where regeneration is seen?

In the liver after a partial hepatectomy 
In the replacement of the epidermis by keratinocytes following a skin burn

136

Are regenerated cells as good as the original cells?

Usually, but not always and not immediately

137

How long does it take regenerated cells to reach morphological and functional maturity?

Weeks, months or years

138

Give an example of when can the time that regenerated cells take to be the same as normal cells be an advantage

In the influenza virus- the virus kills the epithelial cells of the upper respiratory tract, but spares the regenerating cells that follow as they do not yet have receptors for the influenza virus

139

How many times can cells regenerate?

Many- how many times has been found to be species dependant, and depend on the maximum life-span of the species

140

What does a longer species life span mean for regeneration?

The more cell divisions can occur

141

What is the number of cell divisions possible called?

The Hayflick number

142

What is the mean Hayflick number in humans?

61.3

143

What is the Hayflick number in humans related to?

The shortening of telomeres

144

What factors induce cells to regenerate?

Growth factors in the microenvironment 
Cell-to-cell communication

145

How is reconstitution different to regeneration?

It is the replacement of a lost part of the body

146

What does reconstitution require?

Coordinated regeneration of several types of cell

147

Can mammals reconstitute a body part?

No, their ability to do so is minimal, with a few exceptions

148

What are the exceptions to mammals inability to undergo reconstitution?

Small blood vessels (capillaries, small arteries and veins) are able to reconstitute
Children less than 4.5 years old have been reported to reconstitute the tip of a finger, if it is cleanly severed and the amputation is beyond the distal phalangeal joint 
Rabbits and cats can repair holes punched in their ears up to a point

149

What is hyperplasia?

When there is an increase in tissue or organ size due to increased cell numbers

150

What is hyperplasia a response to?

Increased functional demand and/or external stimulation

151

Where can hyperplasia occur?

Only in labile or stabile cell populations

152

What does hyperplasia remain under?

Physiological control

153

Is hyperplasia reversible?

Yes

154

How does hyperplasia differ from regeneration?

They are biologically similar, but differs in that it leads to an increase in the size of the tissue or organ

155

What are the types of physiological hyperplasia?

Hormonal or compensatory

156

What is the result of hormonal hyperplasia?

An increase in functional capacity

157

What is the result of compensatory hyperplasia?

There is an increase in tissue mass after damage

158

What can hyperplasia occur secondary to?

A pathological cause

159

What is the cellular proliferation a normal response to when hyperplasia is secondary to a pathology cause?

Another abnormal condition

160

How does pathological hyperplasia usually occur?

Secondary to excessive hormonal stimulation or growth factor production

161

What is a risk in hyperplastic tissue?

Neoplasia

162

Why is neoplasia a risk in hyperplastic tissue?

As the repeated cell divisions that occur in hyperplasia expose the cell to the risk of mutations (which commonly occur during DNA replication)

163

Give 2 examples of physiological hyperplasia?

Increased bone marrow production of erythrocytes in response to low oxygen 
Proliferation of the endometrium under the influence of oestrogen

164

Give 2 examples of pathological hyperplasia

Epidermal thickening in chronic eczema or psoriasis 
Enlargement of thyroid gland in response to iodine deficiency

165

What is hypertrophy?

An increase in tissue or organ size due to an increase in cell size, without an increase in cell numbers

166

How do cells become bigger in hypertrophy?

Because they contain more structural components
NOT due to swelling

167

Where can hypertrophy occur?

In many tissues, but seen especially in permanent cell populations

168

Why is hypertrophy seen particularly in permanent cell populations?

As these populations have little or no replicative potential, and so any increase in organ size must occur via hypertrophy

169

What does knowing the regenerating capacity of each cell type enable you to do?

Predict the type of response to increased functional demand

170

What is hypertrophy a response to?

Increased functional demand and/or hormonal stimulation

171

What are cells undergoing hypertrophy and hyperplasia doing?

Synthesising more cytoplasm (i.e. protein)

172

What do hypertrophic cells contain?

More structural components

173

What is the result of hypertrophic cells containing more structural components?

The cellular workload is shared by a greater mass of cellular components

174

Can hypertrophy occur in cells where division is possible?

It can, but often occurs alongside hyperplasia

175

What is true of cases where hyperplasia and hypertrophy occur simultaneously?

They are triggered by the same stimulus

176

What does endocrine stimulation usually result in?

A combination of hypertrophy and hyperplasia

177

Give 2 examples of physiological hypertrophy

Skeletal muscle hypertrophy of a body builder
Smooth muscle hypertrophy of a pregnant uterus

178

How much does the uterus enlarge in pregnancy?

~70%

179

What is the enlargement of the uterus in pregnancy under the influence of?

Oestrogen

180

Give two examples of pathological hypertrophy

Ventricular cardiac muscle hypertrophy 
Smooth muscle hypertrophy above an intestinal stenosis 
Bladder smooth muscle hypertrophy with bladder obstruction due to an enlarged prostate gland

181

What causes ventricular muscle hypertrophy?

Response to systemic hypertension or valvular disease

182

What causes smooth muscle hypertrophy above an intestinal stenosis?

The extra work of pushing the intestinal contents through the narrowing

183

Where does hypertrophy of the cardiac muscle occur physiologically?

In athletes

184

Why is hypertrophy in the heart in athletes not pathological?

Because with exercise, unlike with hypertension or valvular heart disease, the heart is under strain for only a few hours/day, and has the rest of the day to recover

185

What is the problem with a pathologically hypertrophic heart?

There is relative anoxia

186

Why is there relative anoxia in a pathologically hypertrophic heart?

Because although the number of capillaries in the heart increases, is it not sufficient to satisfy the increased muscle mass

187

What is the result of the cell damage due to anoxia?

Fibrosis is often seen in pathologically hypertrophic hearts

188

What is the result of fibrosis in the heart?

It decreases the compliance of the cardiac muscle, and therefore its effectiveness

189

What does progressive pathological cardiac hypertrophy eventually lead to?

Myocardial exhaustion

190

What is a simple way to study the effect of functional overstrain?

To remove one of the two paired organs, e.g. if one kidney is removed, the other enlarges, leading to compensatory hypertrophy

191

What happens when the stimulus for hypertrophy and hyperplasia disappears?

The cells and organs become normal size again

192

What happens when there is excessive nutrition?

There is an increase in fat and an increase in protein synthesis

193

Why is obesity in children especially problematic?

Because once fat cells are made, they are with us for life- fat cells acquired at an early age will be there for life

194

What is atrophy?

Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells

195

What results in atrophy?

A reduced supply of growth factors and/or nutrients

196

How can atrophy be considered?

From two perspectives- at the level of the cell, and at the level of the organ/tissue

197

What is cellular atrophy?

A decrease in cell size

198

What is organ/tissue atrophy due to?

Typically, a combination of cellular atrophy and apoptosis

199

When does organ/tissue atrophy occur?

When many cells in the tissue undergo atrophy and apoptosis

200

What does cellular atrophy involve?

Shrinkage in the size of the cell to a size at which survival is still possible

201

How does an atrophic cell differ from a normal one?

It contains a reduced number of structural components, and has reduced function

202

What is atrophy a form of?

Adaptive response which may result in cell death

203

How can atrophy occur?

Cell deletion or cell shrinkage

204

What does wether atrophy occurs by cell deletion or cell shrinkage depend on?

The type of tissue involved

205

What happens when cell deletion occurs?

Certain cells are picked out and induced to perform apoptosis

206

What happens to cell remnants left after apoptosis?

If they are situated on an external surface, they will be lost into the lumen, or from the surface of the body
Otherwise, they will be removed by phagocytosis, either by macrophages or by neighbouring cells

207

What happens in organs undergoing atrophy by cell deletion?

Parenchymal cells will disappear before stromal cells

208

What is the result of parenchymal cells disappearing before stromal cells in organs undergoing atrophy?

These organs often contain a large amount of connective tissue

209

Why does cell shrinkage have limits?

Because most cellular organelles are essential for survival

210

What can be pared down in cell shrinkage?

Some non-essential organelles, e.g. fibrillar material can be lost by skeletal muscle

211

How does cell shrinkage occur?

By self digestion

212

What happens when cell shrinkage occurs by self-digestion?

Residual bodies are seen within cells

213

What are the residual bodies found in cells that have shrunk?

Autophagosomes, which contain lipofuscin and the remains of organelles that can’t be further digested

214

How is ubiquitin involved in cell shrinkage?

It is involved in the process by binding with proteins that are to be removed and therefore targeting them for destruction

215

Can extracellular matrix be lost in atrophy?

Yes

216

What is bone atrophy, or osteoporosis?

Loss of bone mass (not bone calcium)

217

What is the major stimulus to bone formation?

Mechanical stress

218

Who can bone atrophy be a problem for?

Bed-ridden patients Astronauts

219

What is atrophy often linked with?

Disease 
Senescence

220

Is atrophy reversible?

Up to a point, but after years or months it is less so, particularly when parachymal cells are replaced by connective tissue

221

How is atrophy best treated?

Removal of the cause

222

Give two examples of physiological atrophy

Ovarian atrophy in post-menopausal women 
The decrease in size of the uterus after parturiton

223

What can cause pathological atrophy?

Reduced functional demand/workload 
Loss of innervation 
Inadequate blood supply 
Inadequate nutrition 
Loss of endocrine stimulation 
Persistant injury 
Ageing 
Pressure 
Occlusion of a secretory duct 
Toxic agents and drugs
X-rays
Immunological mechanisms

224

What is atrophy due to reduced functional demand/workload known as?

Atrophy of disuse

225

When may atrophy of disuse occur?

Due to immobilisation in a plaster cast

226

Is atrophy due to immobilisation reversible?

Yes, with activity

227

How can protein loss be reduced with immobilisation in a plaster cast?

By passive mechanical stretching and electrical stimulation

228

Where are the principals preventing protein loss in immobilisation used?

Physiotherapy

229

What is atrophy due to loss of innervation called?

Denervation atrophy

230

Give an example of denervation atrophy

Wasted striated muscle within the hand after median (motor) nerve damage

231

What can sensory nerve denervation cause?

Some degree of atrophy within the hands and feet

232

What happens with sensory nerve denervation?

The skin becomes thinner (atrophic) and scaly, and the nails become course and brittle

233

Give an example of atrophy caused by inadequate blood supply?

Thinning of ski on legs with peripheral vascular disease

234

When does inadequate blood supply result in tissue atrophy?

When there is partial but prolonged inadequacy of blood flow

235

Give an example of atrophy caused by inadequate nutrition

Wasting of muscles with malnutrition

236

What happens in inadequate nutrition?

Adipocytes shrink dramatically

237

Which tissue is least susceptible to starvation induced atrophy in adults?

The brain

238

Give two examples of atrophy caused by loss of endocrine stimulation?

Occurs in the breast and reproductive organs with withdrawal of hormonal stimulation
Wasting of the adrenal gland with loss of pituitary ACTH following hypophysectomy

239

What is the best way to shut down and atrophy an endocrine gland?

Give doses of the glands own hormone

240

Give an example of where persistent injury can cause atrophy?

Polymyositis

241

What is polymyositis?

Inflammation of the muscle

242

What is atrophy due to ageing called?

Senile atrophy

243

Where does senile atrophy usually occur?

In permanent tissues

244

Give 6 things affected by senile atrophy

Brain 
Heart
Liver
Kidneys 
Spleen 
Immune system

245

What happens to the liver, kidneys and spleen with senile atrophy?

Their weight is reduced

246

What happens to the immune system with senile atrophy?

It becomes less responsive

247

What is the reason for senile atrophy?

Seems more complex than the Hayflick number
Could involve the progressive accumulation of somatic mutations, so as the system can no longer function

248

What could the progressive accumulation of somatic mutations occur secondary to?

Free radical damage

249

Give two examples of where pressure can cause atrophy

Tissues around an enlarging benign tumour, such as the cerebral hemisphere adjacent to a meningioma 
Thoracic aortic aneurysms can press against the sternum and erode through it

250

What can be seen when a thoracic aortic aneurysm can eroded through the sternum?

A pulsatile mass beneath the skin

251

Why does occlusion of a secretory duct cause atrophy?

It causes the parenchymal cells of the gland to undergo apoptosis

252

Give an example of atrophy due to occlusion of a secretory duct

In the pancreas ligation of the main duct, or blockage of the main duct by a stone, results in the disappearance of the exocrine glands of the pancreas alone.

253

What is the result of the disappearance of the exocrine glands of the pancreas?

The pancreas then appears as a mass of connective tissue contain larger ducts and intact islets of Langerhans

254

What is an exception to occlusion of a secretory duct causing atrophy?

The testis after ligation of the vas deferens

255

What is the result of the ligation of the vas deferns not causing atrophy?

Vasectomies can be successfully reversed

256

Where can become atrophic due to toxic agents and drugs?

Bone marrow
Testes

257

How do x-rays cause atrophy?

By direct cellular damage and microcirculatory damage

258

Give an example of where an immunological mechanism causes atrophy?

Atrophic gastic mucosa in pernicious anaemia

259

How does atrophic gastric mucosa in pernicious anaemia arise?

The body produces autoantibodies against parietal cells. The parietal cells produce intrinsic factor, which is required for absorption of vitamin B12. Lack of vitamin B12 results in anaemia

260

What is metaplasia?

Reversible replacement of one adult differentiated cell type by another of a different type

261

What happens in metaplasia?

Cells of one phenotype are eliminated, and replaced by cells of a different phenotype

262

How is the phenotype of cells changed in metaplasia?

The stem cells within the tissue are reprogrammed and switch to producing a different type of progeny

263

What can metaplasia be considered as?

Abnormal regeneration

264

Where does metaplasia occur in adult mammals?

Only within varieties of epithelia, and within varieties of connective tissue

265

Why could it be seen as surprising that metaplasia only occurs within epithelia and connective tissue?

Because all cells have the same full complement of genetic material, and therefore the potential to form any cell type

266

Is there metaplasia across germ layers?

None proven

267

Is there metaplasia from a connective tissue to epithelium?

Not proven

268

What cell populations does metaplasia occur in?

Only those can replicate- it is not known to occur in adult striated muscle or in neurones

269

What does metaplasia involve?

Expression of a new genetic programme- turning on certain genes, and turning certain genes off

270

What does expression of a new genetic programme result in?

Cells assuming a different structure and different function

271

What does metaplasia occur secondary to?

Signals from molecules such as cytokines and growth factors

272

What is metaplasia often induced by?

Stimuli that cause cell proliferation, e.g. chemical or mechanical irritants

273

What is the end result of metaplasia?

To change one cell type to another more suited to the altered environment

274

Where is metaplasia most commonly seen?

In epithelial tissue 
In columnar epithelium

275

Why do columnar epithelium undergo metaplasia?

They are fragile, so they turn into more resilient squamous epithelium

276

Where is epithelial metaplasia common?

On surface linings

277

Why is epithelial metaplasia common on surface linings?

Because they are exposed to insults

278

What may happen to metaplastic epithelium?

It may loose functions that the original epithelium performed

279

Give an example of where metaplastic epithelium has lost function?

Mucus secretion is lost when columnar epithelium becomes squamous epithelium

280

How does metaplastic epithelium differ from dysplastic epithelium?

Metaplastic epithelium is fully differentiated 
Dysplastic epithelium has disorganised and abnormal differentiated

281

How is cancerous epithelium different from metaplastic epithelium?

It is disorganised, abnormal and irreversible

282

Is metaplasia a good thing?

It can sometimes be adaptive and useful 
However, can be of no apparent use, and may be detrimental

283

Give two examples of where metaplasia can be adaptive and useful

If the bone marrow is destroyed by disease, splenic tissue undergoes metaplasia to bone marrow 
The conversion of columnar epithelium lining ducts to stratified squamous epithelium

284

What is it called when splenic tissue undergoes metaplasia to bone marrow?

Myeloid metaplasia

285

Which ducts may have columnar epithelium thats converted to stratified squamous epithelium?

Salivary glands 
Pancreas
Bile ducts 
Renal pelvis

286

Why may the lining of ducts change to squamous epithelium?

Secondary to chronic irritation to stones

287

What is the advantage of the conversion of columnar epithelial lining to stratified squamous?

As stratified squamous is more resistant to mechanical abrasion

288

Give three examples of when metaplasia can be detrimental

Transformation of bronchial pseudostratified ciliated columnar epithelium to stratified squamous epithelium 
Flat, non- secreting epithelium can be replaced by secretory epithelium or glands such as in the lower oesophagus when the oesophageal stratified squamous epithelium changes to gastric or intestinal type epithelium
When connective tissue changes to bone

289

What does bronchial pseudostratified ciliated columnar epithelium change to stratified squamous epithelium in response to?

The effect of cigarette smoke

290

What is the problem with the transformation of bronchial pseudostratified ciliated columnar epithelium to stratified squamous epithelium?

The squamous epithelium doesn’t produce cleansing mucus, and lacks cilia to move the mucus along

291

When may oesophageal stratified squamous epithelium change to gastric or intestinal type epithelium?

With persistent acid reflux

292

What is persistent acid reflux called?

Barrett’s oesophagus

293

When can metaplastic develop?

In skeletal muscle following trauma, when fibroblasts within the muscle tissue undergo metaplastic change to osteoblasts

294

What is the development of metaplastic bone called?

Traumatic myositis ossificans

295

Where is traumatic myositis ossificans often seem?

In young people, usually after premature return to activity before proper healing has occured

296

What often happens to traumatic myositis ossificans?

It disappears by metaplasia in the opposite direction

297

What can metaplasia sometimes be a prelude to?

Dysplasia and cancer

298

Give two types of epithelial metaplasia that predispose to epithelial cancers

Barrett’s epithelium 
Intestinal metaplasia of the stomach

299

When odes intestinal metaplasia of the stomach occur?

With chronic infection by Helicobacter pylori

300

What is aplasia?

The complete failure of a specific tissue or organ develop

301

What kind of disorder is aplasia?

Embryonic developmental

302

Give two examples of aplasia

Thymic aplasia 
Aplasia of a kidney

303

What does thymic aplasia result in?

Infections and auto-immune problems

304

Other than an embryonic developmental disorder, what is aplasia also used to describe?

An organ whose cells have ceased to proliferate

305

Give an example of aplasia when cells have ceased to proliferate

Aplasia of the bone marrow in aplastic anaemia

306

What is involution?

The normal programmed shrinkage of an organ

307

What does the term involution overlap with?

Atrophy

308

Give 3 examples of involution

Uterus after childbirth 
Thymus in early life 
Temporary foetal organs, usch as the pro- and mesonephros

309

What is hypoplasia?

The congenital underdevelopment or incomplete development of a tissue or organ

310

What has happened in hypoplasia?

There is an inadequate number of cells within the tissue which is present

311

What kind of disorder is hypoplasia?

Embryonic developmental

312

Give 4 examples of hypoplasia

Renal hypoplasia 
Breast hypolasia 
Testicular hypoplasia 
Hypoplasia of the chambers of heart

313

Where does testicular hypoplasia occur?

Klinefelter’s syndrome

314

Why is hypoplasia not the opposite of hyperplasia?

Because it is a congenital condition

315

What is atresia?

The congenital imperforation of an opening

316

Give two examples of atresia?

Atresia of anus or vagina

317

What is dysplasia?

The abnormal mutation of cells within a tissue

318

Is dysplasia reversible?

Potentially

319

What is the problem with dysplasia?

it is often a precancerous condition