Cell Injury and Acute Inflammation

Question 1

What are the six causes of cell stress and injury?

Answer 1

B iological (lack of growth factors)
I mmunological (autoimmune reactions)
G enetic derangements (variations in genetic makeup)
C hemical (pH extremes)
P hysical (trauma)
N utritional imbalances (anorexia nervosa)

Question 2

Which six things occur simultaneously during cell injury to individual cells?

Answer 2

Reduced energy production
Damaged cell membranes
Increased cytosolic Ca2+ concentration
Damage due to free radicals
Damage to proteins
Damage to nuclear/mitochondrial DNA

Question 3

Which three things do damaged cell membranes directly affect?

Answer 3

Mitochondria: mitochondria permeability transition which prevents oxidative phosphorylation and causes apoptosis via cytochrome c
Lysosyme: enzymatic digestion of cell contents
Plasma membrane: loss of cellular contents

Question 4

What affect does reduced energy production have on the cell?

Answer 4

Loss of ATP-dependent cell functions

Question 5

What affect does increased Ca2+ have on the cell?

Answer 5

Destructive Ca2+ enzymes which cause protein breakdown and DNA damage

Question 6

How do free radicals cause damage?

Answer 6

They attack bonds and oxidise things. Oxidative stress occurs when the there are too many free radicals for the cell to cope with

Question 7

Which things occur alongside stress and damage to the cell?

Answer 7

Activation of heat shock factors and stress kinases
Activation of specific signalling proteins:
p53-apoptosis
BMF-actin cytoskeleton damage
Bim-microtubule damage
Bad-don’t have enough growth factors

Question 8

What are the four ways that cells adapt to mild injurious agents/stress?

Answer 8

Hypertrophy: Increased size of cells
Hyperplasia: Increased number of cells
Atrophy: Cell shrinkage
Metaplasia: Reversibly changing from one cell type to another

Question 9

What are the key components of necrosis?

Answer 9

Passive (no energy required)
Autolysis induces inflammatory response
Always pathological
Debris can cause precipitation of calcium caused dystrophic calcification
Chromatin cleaved and condensed (pyknosis)

Question 10

What are the key components of apoptosis?

Answer 10

Requires energy
Common after DNA damage
No inflammation
Meditated by caspases
Chromatin cleaved and condensed (pyknosis)

Question 11

Describe the process of acute inflammation

Answer 11

1. Pro-inflammatory substances activate resident macrophages and endothelial cells
2. Activated endothelial cells produce inflammatory cytokines, prostaglandins and NO which vasodilate and increase permeability of blood vessels
3. Hyperaemia, exudation and oedema occur. Fibrinogen is converted to fibrin and forms dense fibrinoue exudate. Stasis and margination of neutrophils occur in post capillary venules.
4. Selectin causes neutrophils to roll along endothelium before integrin expression is increase and attach to addressin molecules that bring neutrophils to adhere.
5. Diapaedesis occurs
6. In tissues, neutrophils and leukocytes (toll-like receptors) are activated
7. Neutrophils move up chemotactic factor gradients which bind to 7-transmembrane G protein coupled receptors on the leukocyte surface which extends filopodia towards the site of injury
8. Neutrophils attack the cause of injury, die and mix with tissue debris forming pus
9. Offending agent is eliminated or chronic inflammation occurs