Cellular Adaptations and Cellular Damage

Question 1

Define cell adaptation

Answer 1

Reversible changes in cells due to changes in environment (pathological or physiological) Changes can be in number, size or type of cell

Question 2

What are the 3 types of cells in terms of proliferative capacity?

Answer 2

Labile cells: continuously divide in adult life e.g. skin

Stable cells: infrequently divide but can divide rapidly if needed e.g. bone

Permanent cells: Never divide in adult life e.g. brain tissue

Question 3

What are the 4 types of cellular adaptation?

Answer 3

Hypertrophy

Hyperplasia

Metaplasia

Atrophy

Question 4

Define hyperplasia

What type of cells does this occur in?

Give some examples of tissues this can occur in

Answer 4

Increase in the number of cells within a tissue (labile or stable cells)

Reversible

• Hormonal= endometrium during menstrual cycle
• Compensatory= e.g. liver after partial hepatectomy
• Pathological= e.g. chronic irritation, excessive growth factor stimulation

Question 5

Define hypertrophy

Answer 5

Increase in cell size (increase in size of structural proteins)

Can occur in any cells, common in:

• Permanent cells experiencing increased demand e.g.
  
  • Skeletal muscle
  • Uterine muscle in pregnancy
  • Pathological: e.g. cardiac muscle

Question 6

Define atrophy

Answer 6

• Reduction in cell size due to a loss of cell substance
• Involves self digestion of organelles (autophagy)
  
  • e.g. ageing (brain), reduced workload, reduced blood supply

Question 7

Define metaplasia

Answer 7

• Reversible change of one mature adult cell type to another
• Adaptive response
• Usually involves epithelium

E.g.

• Normal: Glandular to squamous epithelium in development of cervix
• Pathological: oesophageal mucosa squamous to columnar epithelium in reflux oesophagitis (Barrett’s oesophagus)

Question 8

What are the types of abnormal cell growth?

Answer 8

Dysplasia

Neoplasia

Question 9

Define agenesis

Answer 9

Failure of differentiation into organ-specific tissue

Question 10

Define dysplasia

Answer 10

Premalignant condition, occurs in labile tissues

• Increased cell growth
• Affects epithelia (e.g. cervix, bladder, stomach)
• Altered differentiation
• Cells mutate in a way that is not recognised by the cells’ regulatory mechanisms
• Can acquire new mutations and become cancerous
• Type of neoplasia

Question 11

Define neoplasia

Answer 11

Abnormal growth of cells that persists after the stimulus has been removed

Cell growth escapes normal regulatory mechanisms:

• Benign
• Malignant- invasion and metastases

Question 12

Define cell injury

Answer 12

Stimulus affecting cell has overwhelmed its capacity to adapt

Question 13

What can cause cell injury and/or death?

Answer 13

• Hypoxia
• Physical agents (e.g. trauma, heat, cold)
• Chemicals and drugs
• Infection
• Immune reactions (e.g. autoimmune, hyper-sensitivity or immunodeficient)
• Genetic derangements
• Nutritional imbalances (excess of insufficiency)

Question 14

Why is ischaemia worse than hypoxia?

Answer 14

Hypoxia is oxygen deprivation (e.g altitude, anaemia)

Ischaemia is oxygen deprivation as well as lack of nutrients; build up of toxins occurs so cell injury is quicker and more severe (e.g. blockage of blood vessel)

Question 15

What are the most common mechanisms of chemical injury to cells?

Answer 15

• Damage to the osmotic environment
• Biochemical cell reactions, e.g. lack of ATP
• Damage to integrity of cell membrane

Question 16

What is Marasmus?

Answer 16

Inadequate calorie intake resulting of metabolism of body tissues, e.g. skeletal muscle

Question 17

What is Kwashiorkor?

Answer 17

Adequate calorie intake but inadequate protein intake

• protein stores in liver depleted
• Liver’s ability to produce proteins is lost
  
  • e.g. albumin, loss of oncotic pressure of blood

Question 18

How does depletion of ATP cause damage to cells?

Answer 18

Loss of oxidative phosphorylation in mitochondria =

• Loss of Na+ pump→influx of Na+ & Ca²⁺, efflux of K⁺→cellular swelling
• Anaerobic glycolysis →acidosis
• Detachment of ribosomes→decreased protein synthesis

Question 19

What can be caused by damage to the mitochondria?

Answer 19

Depletion of ATP

Generation of reactive oxygen species

Damage to mitochondrial membrane = membrane proteins released into cytosol causing cell apoptosis

Question 20

How can increased Ca²⁺ concentrations in cell cytoplasm cause damage?

Answer 20

Activates enzymes which break down cell membrane

Damage to DNA
ATP depletion

Can directly activate enzymes responsible for apoptosis

Question 21

What causes free radical production?

Answer 21

Absorption of radiant energy (e.g. UV light)

Enzymatic metabolism of chemicals (e.g. carbon tetrachloride)

Inflammation

Question 22

How are free radicals removed?

Answer 22

Antioxidants

Storage proteins (e.g. ferritin, transferrin)

Enzymes (e.g. catalase)

Question 23

How do free radicals cause damage?

Answer 23

Direct DNA strand damage

Interaction with proteins

Membrane lipid peroxidation→autocatalytic chain reaction

Question 24

What are the 2 types of cell death?

Answer 24

Necrosis

• Always abnormal, pathological
• Unregulated
• Enzymatic cell digestion→ contents leak out

Apoptosis

• Normal (pathological or physiological)
• Internally controlled
• Nuclear dissolution

Question 25

What are the different types of necrosis?

Answer 25

* **Coagulative:** * Ischaemia * Cells die but substructure of tissue is maintained (e.g. kidney) * No enzymatic digestion of cells * **Liquefactive:** * Dead tissue replaced by liquid material * Enzymatic digestion of cells * Usually caused by inflammation, not usually ischaemic except in brain * **Caseous:** e.g. tuberculosis * **Fat:** Enzymes access and digest fat cells, e.g. pancreatitis * **Infarction:** Ischaemic necrosis due to reduced blood supply * White: blockage of arterial supply * Red: blockage of venous supply

Question 26

Give some examples of physiological and pathological apoptosis

Answer 26

_Physiological:_ * Embyrogenesis * Involution of hormone dependent tissue * Cell loss in proliferative cell populations * Elimination of potentially harmful lymphocytes * Cells no longer required _Pathological:_ * Cells with DNA damage, or endoplasmic reticulum stress * Pathological atrophy if a duct is obstructed * Virus infected cells

Question 27

How does apoptosis occur?

Answer 27

Imbalance between anti-apoptotic and pro-apoptotic molecules in the cell * Activation of caspases * DNA and protein breakdown * Recognition by macrophages

Question 28

What disorders can be caused by dysregulated apoptosis?

Answer 28

**Defective apoptosis with increased survival:** * Autoimmune * Neoplastic **Defective apoptosis with decreased survival:** * Ischaemic injury * Death of virus infected cells