Cell Response to Injury: Ultra-structural Changes

Question 1

what causes cell injury?

Answer 1

Results from disruption of structure and function of sub-cellular components

Question 2

what are the consequences of cell injury?

Answer 2

damage to cellular components

Question 3

where is the damage seen?

Answer 3

• Mitochondria
• Plasma membrane
• Lysosomes
• Nucleus

Question 4

what can damage the mitochondria?

Answer 4

Hypoxia, hypoglycaemia & toxins

Question 5

how are mitochondria damaged?

Answer 5

• Development of vacuoles

* Cristae become damaged

Question 6

what does a decrease in oxidative phosphorylation lead to?

Answer 6

Reduced levels of ATP

Question 7

what is reduced ATP level known as?

Answer 7

low amplitude swelling

Question 8

can low amplitude swelling be reversed?

Answer 8

yes

Question 9

what are the effects of reduced ATP?

Answer 9

• Reduced activity of Na pump which leads to changes in Na+ and K+ concentration
• Net influx of H2O across plasma membrane which leads to swelling
• Failure of intracellular Ca2+ homeostasis

Question 10

Why is Ca2+ concentration in cytosol low?

Answer 10

Ca2+ activates cytosolic enzymes

Question 11

Which enzymes keep calcium levels in check?

Answer 11

ATP dependent enzymes

Question 12

What does a reduction in cellular ATP lead to in terms of calcium levels?

Answer 12

It leads to increase intracellular calcium

Question 13

what does intracellular calcium increase lead to?

Answer 13

Activation of:
• Phospholipases
• Endonucleases
• Proteases

Question 14

how is plasma membrane damage caused?

Answer 14

The damaged mitochondria lead to reduced ATP which leads to reduced activity of the Na pump and a net influx of H2O into the cell, which causes cellular swelling and the formation of blebs

Question 15

what does the disruption of membrane lead to?

Answer 15

the leakage of enzymes

Question 16

what does leakage of enzymes lead to?

Answer 16

Activation of acid hydrolases:
• RNAases
• DNAases
• Proteases

Enzymatic digestion/irreversible damage

Question 17

If acid hydrolases are activated which pathway of cell death will occur?

Answer 17

Necrosis

Question 18

how is the endoplasmic reticulum damaged?

Answer 18

• Vacuolation and swelling seen early in injury

* Prolonged injury leads to detachment of ribosomes

Question 19

what does ribosome detachment result in?

Answer 19

Decreased protein synthesis

Question 20

how can the nucleus be damaged?

Answer 20

• Invagination of nuclear membrane
• Chromatin clumping
• Distinct nuclear changes

Question 21

what are the features of necrosis?

Answer 21

• Loss of membrane integrity/enzymatic destruction
• Leakage of cellular constituents
• Inflammatory response
• Necrotic cell changes reflect key processes

Question 22

Why do cells that have undergone necrosis stain pink with H&E?

Answer 22

• Demonstrate denatured and coagulation of protein

* Loss of cytoplasmic RNA

Question 23

What are the features of cells that lose definition?

Answer 23

• Loss of organelles
• Enzyme digestion: phospholipases and proteases
• Replacement of dead cells: myelin figures and calcium deposition

Question 24

what is Pkynosis?

Answer 24

nuclear shrinkage

Question 25

what is Karyorrhexis?

Answer 25

nuclear fragmentation

Question 26

what is Karyolysis?

Answer 26

nuclear disintegration

Question 27

what are the distinct nuclear changes?

Answer 27

pkynosis, kerhyorrhexis, Karyolysis

Question 28

what can be seen in a normal cell (stages of necrosis)?

Answer 28

distinct nucleus and nucleolus cytoplasm:pale pink/purple due to cellular RNA in rough endoplasmic reticulum

Question 29

what are the features of an early necrotic cell (stages of necrosis)?

Answer 29

cytoplasm shrinks and increase in eosinophilia (pink staining) - loss of ribosomes nucleus shrinks and basophilic (purple) cessation DNA transcription

Question 30

what happens to the cell as necrosis occurs?

Answer 30

after early necrotic cell features:- the cell remains small and eosinophilic and the cell membrane breakdown results in irregular shape and karyorrhexis occurs finally the cell is partly denatured mass protein and the cytoplasm is eosinophilic and the nucleus completely dissolves

Question 31

what are the features of apoptosis?

Answer 31

* Programmed cell death – induced by a tightly regulated suicide programme * Deletion of individual cells * No inflammatory response

Question 32

what do apoptotic cell changes involve?

Answer 32

* Cells shrink – dense cytoplasm, more tightly packed organelles * Chromatin condensation – aggregation chromatin under nuclear membrane; fragmentation of nucleus * Formation of blebs and apoptotic bodies – extensive surface blebbing leads to fragmentation * Phagocytosis of apoptotic bodies by macrophages