Week 1 Pathology - Cell Injury and Adaption

Question 1

Define hypertrophy?

Examples?

Answer 1

Increase in cellular size, resulting increased size of affected organ (with no new cells)

Physiological = muscle, uterus in pregnancy

Pathological = cardiac remodelling in heart failure

Question 2

Define hyperplasia?

Examples?

Answer 2

Increase in numbers of cells in organ/tissue in response to stimulus.

Physiological = breast breast glandular epithelium during puberty

Pathological = BPH, cancer

Others: liver regeneration post resection,

Question 3

Define atrophy?

Examples?

Answer 3

Reduction in size of an organ/tissue due to decrease in cell size or number.

Physiological = embryonic structures (i.e. thyroglossal duct)

Pathological = decreased workload, ischaemic injury, inadequate nutrition, loss of hormonal stimulation (menopause) or denervation

Question 4

During atrophy, what mechanisms occur with cells attempting to survive?

Answer 4

Decrease in cell size and organelles, with decreased protein synthesis - aimed at reducing metabolic demand of cells to sufficiently permit survival

Question 5

Define metaplasia?

Examples?

Answer 5

REVERSIBLE change from one differentiated cell type to another, as an adaptive response to cellular stresses associated with tissue damage, repair and regeneration

Examples = columnar to squamous epithelium in respiratory tract with smoking, stratified squamous to columnar epithelium with goblet cells

Question 6

Define dysplasia?

Examples?

Answer 6

Presence of cells of abnormal type within tissue, may signify stage preceding malignancy.

Example = cervical dysplasia post HPV infection.

Characterised by loss of uniformity of individual cells and loss architectural orientations

Question 7

Define reversible cell injury?

Answer 7

Cellular stress leading to reversible functional and morphological changes to cell, which will revert when stimulus is removed

Question 8

What is reversible cellular injury defined by?

Answer 8

Reduced oxidative phosphorylation and ATP depletion, leading to cellular swelling and changes in ion concentrations and water influx

Morphology:
- Swelling of cell and organelles
- Blebbing, loss of microvilli
- Dilation and detachment of ribosomes from ER
- Clumping of nuclear chromatin

Question 9

What are causes of cellular injury?

Answer 9

1) Hypoxia: (Ischaemia, inadequate oxygenation of blood, decreased oxygen carrying capacity of blood)
2) Physical Agents: (mechanical trauma, burns, radiation, electric injury)
3) Chemical agents
4) Infection
5) Immunological
6) Genetic

Question 10

What are the different mechanisms of cellular injury?

Answer 10

1) Depletion of ATP

2) Mitochondrial damage

3) Ca2+ influx/loss of homeostasis

4) Accumulation of O2 free radicals

5) Defects in membrane permeability

6) DNA damage

Question 11

What are the specific effects of oxygen free radicals?

Answer 11

React with:
- Fatty acids, disruption of plasma membrane, organelles
- Proteins: oxidation, loss of enzymatic activity, abnormal folding
- DNA: oxidation, mutations, breaks –> unable to carry out normal cellular function

Question 12

How does a cell normally deal with superoxide?

Answer 12

In mitochondria, ‘SOD’ (superoxide dimutase) converts to H2O2 (hydrogen peroxide) which is either acted on by glutathione peroxidase or catalase to convert to H20 and O2.

Question 13

In what conditions do you see increased activity of oxygen derived free radicals?

Answer 13

Chemical/radiation injury
Reperfusion injury
Microbial killing by phagocytes

Question 14

What are the two types of cell death?

Answer 14

Apoptosis
Necrosis

Question 15

What are the features of necrosis?

Answer 15

“Uncontrolled cell death” characterised by inflammatory reaction following.

Features:
- Increased cell size
- Nucleus = pkynosis –> karyorrhexis –> karylosis
- Disrupted cellular membrane
- Leakage of cellular contents
- Always pathological

Question 16

What are the features of apoptosis?

Answer 16

Cell size is reduced, intact plasma membrane, intact cellular contents released via apoptotic bodies, no inflammation.

Generally physiological process aimed to eliminate unwanted or damaged cells in a controlled manner. “Programmed cell death”

Question 17

What are examples of apoptosis in normal physiology?

Answer 17

• Programmed destruction of cells in embryogenesis
• Involution of hormone dependent tissues (endometrium during menstruation)
• Cell loss in proliferating populations (immature lymphocytes fail to produce useful antigen receptors)
• Elimination of potentially self reactive lymphocytes
• Death of cells that have served a useful purpose (i.e. neutrophils post acute inflammatory response)

Question 18

What are the two pathways for initiation of apoptosis?

Answer 18

Intrinsic vs extrinsic

Question 19

What dictates the initiation of the intrinsic pathway of apoptosis?

Answer 19

Increased mitochondrial permeability and release of pro-apoptotic molecules into cytoplasm –> culminating in caspase cascade –> apoptosis

Question 20

What is the extrinsic pathway for apoptosis?

Answer 20

engagement of plasma membrane death receptors on variety of cells (i.e. Type 1 TNF and Fas) which when bound by Fas Ligand –> activation of caspase pathway and apoptosis

Question 21

Describe coagulative necrosis?

Answer 21

Architecture of cells is preserved for a span of days, enucleated, eosinophilic cells

Caused by ischaemic blockage of a vessel supplying tissues (except brain)

Question 22

Describe liquefactive necrosis?.

Answer 22

Digestion of dead cells, transformation of tissue into liquid, viscous mass

Creamy yellow because of presence of dead leukocytes (pus)

Caused by bacterial/fungal infections

Question 23

Define gangrenous necrosis?

Answer 23

Typically applied to necrosis of a limb, where coagulative necrosis has involved multiple tissue planes –> if superimposed bacterial infection, wet gangrene (superimposed liquefactive necrosis)

Question 24

What diseases is caseous necrosis seen?

Answer 24

TB granulomas, Crohn’s –> lysed cells within distinctive inflammatory border

Question 25

When does fat necrosis occur?

Answer 25

Acute pancreatitis

Focal areas of fat destruction from release of activated pancreatic lipase into the substance of the pancreas and the peritoneal cavity.

Morphology = fat combining with calcium to form chalky white areas

Question 26

What conditions is fibrinoid necrosis seen?

Answer 26

Autoimmune reactions involving blood vessels –> antibody/antigen complexes deposition with vessel walls and leading to vasculitis syndrome: RA, SLE

Question 27

What is reperfusion injury?

Answer 27

Restoration of blood flow to ischaemic tissues, where cells have undergone reversible cell injury.

Injured cells trigger further inflammation causing further cell loss in addition to those that had already been irreversibly damaged.

Question 28

What are suggested mechanisms of reperfusion injury?

Answer 28

1. Generation of reactive oxygen species
2. Cytokines generated from inflammatory response from necrosis –> neutrophil recruitment at site
3. Complement system activation
4. Intracellular calcium overload

Question 29

What is pathological calcification?

Answer 29

Abnormal tissue deposition of calcium salts, iron, magnesium and other mineral salts

Question 30

What is the difference between metastatic and dystrophic calcification?

Answer 30

Dystrophic = deposition in locally dying tissues, in the setting of normal serum levels and no derangement of calcium metabolism

Metastatic = deposition in normal tissues, secondary to hypercalcaemia/derangement of calcium metabolism