Lecture 16: How Cells Respond to Injury

Question 1

what are the basic ways of tissue growth

Answer 1

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

Question 2

labile cells

Answer 2

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

Question 3

permanent cells

Answer 3

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

Question 4

how can a tissue adapt in response to injury

Answer 4

• hypertrophy
• hyperplasia
• atrophy
• metaplasia

Question 5

what is hypertrophy

Answer 5

• 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

Question 6

what are examples of physiological hypertrophy

Answer 6

• hypertrophy of skeletal muscle through training

- hormonal stimulation causes uterine hypertrophy

Question 7

what are examples of pathological hypertrophy

Answer 7

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

Question 8

what is hyperplasia

Answer 8

• 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

Question 9

what are examples of physiological hyperplasia

Answer 9

• hormonal hyperplasia of breast tissue during breastfeeding

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

Question 10

what are examples of pathological hyperplasia

Answer 10

usually due to excess hormone

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

Question 11

what is atrophy and what is the mechanism

Answer 11

• reduction in cell size and numbers

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

Question 12

what are examples of physiological atrophy

Answer 12

• 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

Question 13

what are examples of pathological atrophy

Answer 13

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

Question 14

what is metaplasia

Answer 14

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

Question 15

what are examples of physiological metaplasia

Answer 15

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

Question 16

what are examples of pathological metaplasia

Answer 16

• 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

Question 17

what happens in reversible cell injury

Answer 17

• 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

Question 18

what happens in irreversible cell injury

Answer 18

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

Question 19

what is necroptosis

Answer 19

shows features of both apoptosis and necrosis

Question 20

what is pyroptosis

Answer 20

apoptosis with fever and IL-1 signalling

Question 21

what happens during apoptosis

Answer 21

• cell fragments into small vesicles called apoptotic bodies

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

Question 22

what happens during necrosis

Answer 22

• 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

Question 23

what happens during coagulative necrosis

Answer 23

• ischaemia

- shape and architecture of the organ is highly preserved

Question 24

what happens during liquefactive necrosis

Answer 24

• mainly seen in brain
• ischaemic
• liquified, viscous, soft lesion
• seen in bacterial infections

Question 25

what happens during caseous necrosis

Answer 25

• “cheese-like” appearance

- usually mycobacterial infections

Question 26

what happens during fibrinoid necrosis

Answer 26

• eg vasculitis

- look for fibrin around blood vessels

Question 27

what happens during gangrenous necrosis

Answer 27

necrosis of a limb

Question 28

why is ischaemia worse than hypoxia

Answer 28

in hypoxia anaerobic respiration can still take place, in ischaemia no waste metabolites can be removed

Question 29

what is ischaemia reperfusion injury

Answer 29

when restoration of blood flow after ischaemia exacerbated tissue damage

Question 30

what are the pathways of apoptosis and what do they both result in

Answer 30

• 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

Question 31

what are examples of physiological apoptosis

Answer 31

• apoptosis in embryogenesis

- menstrual cycle

Question 32

what happens to cause pathological apoptosis

Answer 32

• DNA damage, eg radiotherapy and chemotherapy
• accumulation of abnormal proteins
• HIV and Hepatitis B
• duct obstrcution, eg in kidney / pancreas

Question 33

what is autophagy associated cell death

Answer 33

• 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