Lecture 16: How Cells Respond to Injury Flashcards

1
Q

what are the basic ways of tissue growth

A
  • multiplicative: increase in cell number
  • auxetic: increase in cell size
  • accretionary: increase in extracellular tissue
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2
Q

labile cells

A
  • continuously proliferate
  • have a short lifespan and rapid turnover time
  • eg blood cells and many epithelial cells esp. in gut
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3
Q

permanent cells

A
  • have very little or no regenerative ability
  • have undergone terminal differentiation
  • eg keratinocytes, neurons, cardiac and skeletal muscle, red blood cells
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4
Q

how can a tissue adapt in response to injury

A
  • hypertrophy
  • hyperplasia
  • atrophy
  • metaplasia
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5
Q

what is hypertrophy

A
  • increase in cell size, and more organelles within the cell
  • is the only adaptive response available to permanent cells
  • happens due to incrased workload, which activates the P13K/AKT and G-coupled pathways to induce hypertrophy
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6
Q

what are examples of physiological hypertrophy

A
  • hypertrophy of skeletal muscle through training

- hormonal stimulation causes uterine hypertrophy

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7
Q

what are examples of pathological hypertrophy

A
  • cardiac hypertrophy due to hypertension or valvular disease
  • bladder hypertrophy due to prostate enlargement
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8
Q

what is hyperplasia

A
  • increase in cell number
  • requires cells to be able to divide, so only happens in labile or stabile cells
  • controlled by growth factor activation and stem cell activation
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9
Q

what are examples of physiological hyperplasia

A
  • hormonal hyperplasia of breast tissue during breastfeeding

- compensatory hyerplasia when tissue is lost, eg in liver resection or bone marrow hyperplasia in bleeding

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10
Q

what are examples of pathological hyperplasia

A

usually due to excess hormone

  • excess oestrogen leads to endometrial hyperplasia
  • excess androgens cause prostatic hyperplasia
  • HPV induced hyperplasia in warts
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11
Q

what is atrophy and what is the mechanism

A
  • reduction in cell size and numbers

- mechanism is by degradation of cellular organelles or proteins by ubiquitin-proteosome pathways

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12
Q

what are examples of physiological atrophy

A
  • testicular or ovarian atrophy due to loss of hormonal stimulation in old age
  • atrophy of uterus after parturition (giving birth)
  • atrophy of developmental structures like the notochord / thyreoglossal duct
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13
Q

what are examples of pathological atrophy

A
  • muscle wastage due to disuse
  • vascular atrophy in the brain due to atherosclerosis
  • malnutrition
  • pressure atrophy on surrounding tissues due to benign tumours
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14
Q

what is metaplasia

A
  • one differentiated cell / tissue type is replaced by another
  • usually seen in epithelium but possible in mesenchyme
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15
Q

what are examples of physiological metaplasia

A
  • metaplasia of cervical columnar epithelium to stratified squamous epithelium in response to vaginal acidic environment
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16
Q

what are examples of pathological metaplasia

A
  • oesophageal stratified squamous epithelium to columnar epithelium in response to acid reflux, called Barrett’s oesophagus
  • bronchial ciliated columnar epithelium to stratified squamous epithelium in response to smoking
  • myositis ossificans within muscles after trauma
17
Q

what happens in reversible cell injury

A
  • reduced oxidative phosphorylation and depletion of ATP so ATP dependent processes stop
  • change in ionic concentrations and influx of water causes swelling
  • changes in intracellular organelles
  • increase in eosinophils in blood
18
Q

what happens in irreversible cell injury

A

reversible cell injury +

  • lysosome rupture and autodigestion of cell
  • proteins denature and membranes rupture
  • nuclear changes like karyolysis, karyorrhexis and pyknosis
  • cell death and cellular components leak into blood
  • levels of these can determine intensity of damage, eg troponin in heart and transaminases in liver
19
Q

what is necroptosis

A

shows features of both apoptosis and necrosis

20
Q

what is pyroptosis

A

apoptosis with fever and IL-1 signalling

21
Q

what happens during apoptosis

A
  • cell fragments into small vesicles called apoptotic bodies

- express proteins on the surface that make them highly visible to phagocytes, which digest them

22
Q

what happens during necrosis

A
  • ATP depletion
  • mitochondrial damage
  • influx of calcium
  • accumulation of oxygen radicals which are highly reactive and break the cell apart
  • increased membrane permeability
  • DNA and protein damage
  • drop in pH due to lactic acid build up
  • cellular constituents leak into surrounding tissues
23
Q

what happens during coagulative necrosis

A
  • ischaemia

- shape and architecture of the organ is highly preserved

24
Q

what happens during liquefactive necrosis

A
  • mainly seen in brain
  • ischaemic
  • liquified, viscous, soft lesion
  • seen in bacterial infections
25
what happens during caseous necrosis
- "cheese-like" appearance | - usually mycobacterial infections
26
what happens during fibrinoid necrosis
- eg vasculitis | - look for fibrin around blood vessels
27
what happens during gangrenous necrosis
necrosis of a limb
28
why is ischaemia worse than hypoxia
in hypoxia anaerobic respiration can still take place, in ischaemia no waste metabolites can be removed
29
what is ischaemia reperfusion injury
when restoration of blood flow after ischaemia exacerbated tissue damage
30
what are the pathways of apoptosis and what do they both result in
- mitochondrial / intrinsic pathway: mediated by BCL-2 proteins, activates cytochrome C - death receptor / extrinsic pathway: surface receptors like TNF and Fas recognise ligands - both activate caspase enzymes and attract phagocytes
31
what are examples of physiological apoptosis
- apoptosis in embryogenesis | - menstrual cycle
32
what happens to cause pathological apoptosis
- DNA damage, eg radiotherapy and chemotherapy - accumulation of abnormal proteins - HIV and Hepatitis B - duct obstrcution, eg in kidney / pancreas
33
what is autophagy associated cell death
- cells cannibalise themselves by lysosomal degradation in nutrient deprivation - may be a response against neoplasia but poorly understood - involved in some neoplasms and chronic idiopathic inflammatory bowel syndromes - TB and herpes infections