2.11 - Cell Injury and Fate

Question 1

Triangle of how cells respond to stress / injury

Answer 1

• normal cell (homeostasis) –(stress, increased demand)–> adaptation –(inability to adapt)–> cell injury –> cell death
• normal cell (homeostasis) –(injurious stimulus)–> cell injury –> cell death
• physiological - occurs in healthy body
• pathological - occurs in disease

Question 2

Types of cell injury

Answer 2

• lethal - produces cell death
• sublethal - produces injury not amounting to cell death; may be reversible or progress to cell death

Question 3

Causes of cell injury

Answer 3

1. oxygen deprivation (–> myocardial infarction)
2. chemical agents
3. infectious agents
4. immunological reactions
5. genetic defects
6. nutritional imbalances
7. physical agents
8. aging

Question 4

What does the cellular response to injurious stimuli depend on?

Answer 4

1. the type of injury
2. its duration
3. its severity

Question 5

What do the consequences of an injurious stimulus depend on?

Answer 5

1. the type of cell
2. its status

Question 6

What four intracellular systems are particularly vulnerable to cell injury?

Answer 6

1. cell membrane integrity
2. ATP generation
3. protein synthesis
4. integrity of the genetic apparatus

Question 7

When do we get morphological changes in cells?

Answer 7

• the structural and biochemical components of a cell are so integrally related that multiple secondary effects rapidly occur
• cellular function is lost before cell death occurs which in turn occurs before the morphological changes are seen
• i.e. morphological changes occur after cell death which happens after loss of cell function

Question 8

What is atrophy? (Cellular adaptation to injury)

Answer 8

• shrinkage in the size of the cell/organ by the loss of cell substance
• e.g. dementia brain - neurones have atrophied –> smaller brain
• e.g. muscle atrophy secondary to denervation (any loss of nerve supply)

Question 9

What is hypertrophy? (Cellular adaptation to injury)

Answer 9

• increase in the size of cells and consequently an increase in the size of the organ
• can be physiological or pathological
• physiological causes - increased functional demand or specific hormonal stimulation e.g. physiological hypertrophy when muscles grow after exercise
• pathological causes - e.g. pathological hypertrophy due to hypertension or valve disorders

Question 10

What is hyperplasia? (Cellular adaptation to injury)

Answer 10

• an increase in the number of cells in an organ
• can be physiological or pathological
• physiological hyperplasia can be either hormonal or compensatory
• pathological hyperplasia is usually due to excessive hormonal or growth factor stimulation
• e.g. of physiological hyperplasia - proliferative endometrium
• e.g. of pathological hyperplasia - carcinoma

Question 11

What is metaplasia? (Cellular adaptation to injury)

Answer 11

• a reversible change in which one adult cell type is replaced by another
• may be physiological or pathological
• e.g. of physiological metaplasia - cervix - normally lined with columnar epithelial cells, switches to squamous during pregnancy, then back to columnar after preganancy
• e.g. of pathological metaplasia - Barrett’s oesophagus - normal oesophagus lined with non-keratinising epithelia and stomach is lined with columnar; acid reflux = stomach acid comes up to oesophagus –> squamous cells become columnar. When the acid reflux goes away, the columnar epithelia switch back to squamous (reversible)

Question 12

What is dysplasia? (Cellular adaptation to injury)

Answer 12

• precancerous cells which show the genetic and cytological features of malignancy but not invading the underlying tissue
• signs that a cell is showing malignancy - big nuclei, increased mitosis
• Barrett’s oesophagus associated dysplasia

Question 13

What are the two microscopic changes associated with reversible injury?

Answer 13

1. fatty change
   - e.g. alcoholic fatty change - after drinking a lot of alcohol, there are white spots of visible fat in hepatocytes in the liver, but when you stop drinking the fat will go away (reversible)
2. cellular swelling
   - e.g. ballooning degradation - cytoskeleton damage causes proteins to accumulate in cells which cause them to swell

• these are examples of degenerative changes i.e. changes associated with cell and tissue damage

Question 14

What is necrosis?

Answer 14

• confluent cell death associated with inflammation
  Four types of necrosis:
  1. coagulative necrosis - when the structure of cells becomes fixed after death e.g. myocardial infarct
  2. liquefactive necrosis - where tissues become liquefied e.g. a characteristic of brain damage since brain does not have much connective tissue to keep the cells in place
  3. caseous necrosis - the cells become structureless and oozy - ‘cheesy’ - e.g. pulmonary TB
  4. fat necrosis - e.g. in pancreas there are many digestive enzymes - if they are activated there instead of the duodenum they can digest pancreatic tissue - this includes lipases liquefying fat which causes fat necrosis into FFAs, which combine with calcium to form precipitates

Question 15

What is apoptosis?

Answer 15

• programmed cell death of individual cells
• bits of the cell bleb off but the cell membrane remains intact to form apoptotic bodies - part of a cell with a little bit of fragmented nucleus and little bit of cytoplasm
• these bodies are picked up by macrophages which dispose of them

Question 16

Causes of apoptosis

Answer 16

1. embryogenesis e.g. fingers initially joined together but split apart when apoptosis of cells joining the digits together occurs
2. deletion of auto-reactive T cells in the thymus - important in preventing autoimmune diseases
3. hormone-dependent physiological involution - e.g. in menstruation, once hormones are removed, massive apoptosis triggers bleeding
4. cell deletion in proliferating populations - how cells die normally in the body
5. a variety of mild injurious stimuli that cause irreparable DNA damage that in turn triggers cell suicide pathways - cells do not want to pass on damaged DNA to progeny so they undergo apoptosis

Question 17

What are the differences between apoptosis and necrosis?

Answer 17

1. apoptosis may be physiological, necrosis is always pathological
2. apoptosis is an active energy dependent process (so cells can maintain membranes and package organelles into apoptotic bodies)
3. apoptosis is not associated with inflammation, unlike the neutrophilic inflammatory response from necrosis
4. apoptosis is usually single cells dying, necrosis can be sheets of cells dying (inflammatory response damage nearby healthy tissue too)
5. apoptosis –> apoptotic bodies = cell membrane does not lose integrity, but necrosis = bits of cell membrane break off so membrane loses integrity and enzyme leakage occurs

Question 18

What is necroptosis?

Answer 18

• programmed cell death associated with inflammation
• various causes e.g. viral infections
• mix of apoptosis (energy dependent) and necrosis (inflammation)