Lecture: Pathology 2: How the cell responds to injury

Question 1

How does tissue grow?

Answer 1

Increase in cell size or number by synthesis of new components. Different tissues show different proliferative ability.

Question 2

What does the term multiplicative mean?

Answer 2

Increase in cell number by mitotic division

Question 3

What does the term auxetic mean?

Answer 3

Increase in cell size

Question 4

What does the term accretionary mean?

Answer 4

Increase in extracellular tissue

Question 5

What is the role of cell turnover?

Answer 5

Cell turnover permits maintenance of continuously growing tissues (e.g. skin, intestinal mucosa) and healing (injury, disease).

Question 6

What are labile cells?

Answer 6

Cells that continuously proliferate, have a short lifespan and a rapid turnover time

Question 7

What are examples of labile cells?

Answer 7

White blood cells and many epithelial cells

Question 8

What are stable cells (facultative dividers)?

Answer 8

Cells that have good regenerative ability but would normally have a low cell turnover

Question 9

What are examples of stable cells?

Answer 9

Quiescent tissues e.g. hepatocytes

Question 10

What are permanent cells?

Answer 10

Cells that have very little or no regenerative ability

Question 11

What are examples of permanent cells?

Answer 11

Terminally differentiated cells, eg. keratinocytes, neurons, cardiac and skeletal muscle, and red blood cells.

Question 12

How do cells acquire specialised functions?

Answer 12

Cells acquire a specialised function and this is a results of selective expression of genes. Disease replicates this process e.g. in neoplasia.

Question 13

What determines severity of cell injury?

Answer 13

Cell injury depends on the duration and severity of the stimulus. Cell injury occurs if cells are so severely stressed that they can no longer adapt.

Question 14

What are the 3 pathways following cell injury?

Answer 14

1. Adapt
2. Reversible cell injury (return to normal)
3. Irreversible cell injury (necrosis or apoptosis)

Question 15

What is hypertrophy?

Answer 15

Increase in cell size owing to increase in structural components; only adaptive response available to permanent cells (e.g. cardiac muscle cells).

Question 16

What are examples of physiological hypertrophy?

Answer 16

• Hypertrophy of skeletal muscle through training

* Uterine hypertrophy owing to hormone stimulation

Question 17

What are examples of pathophysiological hypertrophy?

Answer 17

• Cardiac hypertrophy owing to hypertension or valvular disease
• Bladder hypertrophy owing to prostatic enlargement

Question 18

How does pathological hyperplasia differ from neoplasia?

Answer 18

Pathological hyperplasia is distinct from neoplasia but increased cell turnover increases the risk of genetic aberrations/mutations and thus neoplasia.

Question 19

What is hyperplasia?

Answer 19

Increase in cell number that requires cells that are able to divide (labile or stable cells).

Question 20

What triggers hyperplasia?

Answer 20

Hyperplasia is triggered by growth factor activation and stem cell activation.

Question 21

What are examples of pathophysiological hyperplasia?

Answer 21

• Endometrial hyperplasia owing to excess oestrogen
• Prostatic hyperplasia owing to excess androgens
• Virus induced hyperplasia in warts (HPV)

Question 22

What are examples of physiological hyperplasia?

Answer 22

• Breast development and breast feeding

* Partial liver resection or bone marrow hyperplasia in bleeding

Question 23

What is atrophy?

Answer 23

Reduction of the size of cells (and cell organelles) and reduction of cell numbers (apoptosis).

Question 24

What triggers atrophy?

Answer 24

Triggered by degradation of cellular organelles/proteins by ubiquitin-proteasome pathways.

Question 25

What are examples of physiological atrophy?

Answer 25

* Atrophy of uterus after parturition | * Atrophy of developmental structures

Question 26

What are examples of pathophysiological atrophy?

Answer 26

* Vascular atrophy of the brain | * Malnutrition / starvation / marasmus

Question 27

What is metaplasia?

Answer 27

Reversible change where one differentiated cell type/tissue is replaced by another differentiated cell type/tissue in response to environmental change. Usually seen in epithelium but possible in mesenchymal tissues.

Question 28

What triggers metaplasia?

Answer 28

Triggered by stem cell differentiation and/or colonization by differentiated cells from nearby tissues.

Question 29

What are examples of pathophysiological metaplasia?

Answer 29

* Metaplasia from bronchial ciliated columnar epithelium to stratified squamous epithelium in response to smoking. * Metaplasia from oesophageal stratified squamous epithelium to columnar epithelium in response to acid reflux (Barrett’s oesophagus).

Question 30

What are examples of physiological metaplasia?

Answer 30

Metaplasia of cervical simple columnar epithelium to stratified squamous epithelium in response to acidic vaginal environment.

Question 31

What is reversible cell injury?

Answer 31

Reversible cell injury results in morphological and cellular changes, however restoration of homeostasis can be achieved when cellular stress is removed.

Question 32

What is apoptosis?

Answer 32

Programmed cell death that does not result in inflammation as cell membrane remains intact but is altered. Normal, however, highly elevated in disease.

Question 33

What is necrosis?

Answer 33

Cell lysis and ingestion by immune cells leading to an immunological response.

Question 34

What are the 4 main characteristics of irreversible cell injury?

Answer 34

1. Lysosome rupture and autodigestion 2. Denaturation of proteins 3. Membranes rupture 4. Nuclear changes

Question 35

How can irreversible cell damage be detected?

Answer 35

Leakage of cellular components from damaged cells into the blood allows for detection of injured tissues

Question 36

What is necroptosis?

Answer 36

Cell death which shows both necrosis and apoptosis features

Question 37

What is pyroptosis?

Answer 37

Apoptosis with fever and IL-1 signalling

Question 38

How is apoptosis activated?

Answer 38

Activation of intracellular caspase enzymes to degrade DNA and proteins which allows for cell membrane to remain in tact but attract phagocytes to degrade cell without triggering immune response. Caspase activated by death receptors and mitochondria-mediated receptors.

Question 39

Examples of physiological apoptosis

Answer 39

Elimination of self-reactive / autoimmune lymphocytes | Programmed apoptosis of inflammatory cells at the end of the inflammatory response

Question 40

Examples of pathophysiological apoptosis

Answer 40

DNA damage of any kind usually triggers apoptosis | Accumulation of abnormal proteins

Question 41

What is ischemia?

Answer 41

Lack of blood flow to tissue and cells

Question 42

What is ischaemia reperfusion injury?

Answer 42

Where restoration of blood flow, after a period of limited blood flow, exacerbates tissue damage.

Question 43

What is autophagy?

Answer 43

Consumption of own tissue by lysosomal degradation | as a survival mechanism in nutrient deprivation

Question 44

What regulates autophagy?

Answer 44

Regulated by autophagy genes