2. Causes and Mechanisms of Cell Injury and Cell Death

Question 1

What are three different types of disease?

Answer 1

Genetic
Acquired
Multifactorial

Question 2

What is the aetiology of genetic disease?

Answer 2

Chromosomal disorders- abnormal numbers and abnormal structures
Prenatally acquired gene disorders - single gene disorders

Question 3

What are the features associated with downs syndrome?

Answer 3

Increased incidence with increasing maternal age 
Congenital Heart Disease
Predesposition to Leukaemia
Early Alzheimer's Disease
Learning Disability

Question 4

What is CF?

Answer 4

Single gene mutation on chromosone 7

A disorder of ion transport in epithelial cells

Question 5

What are features of CF?

Answer 5

Alteration in the mucus produced at epithelial surfaces
Thick mucus plugs ducts and tubules of glands
High sweat sodium and chloride concentration
Chronic Lung Disease
Pancreatic insufficiency
Malnutrition
Male Infertility

Question 6

What is significant about autosomal dominant inherited single gene disorder?

Answer 6

the defective product of the gene is usually a structural protein, not an enzyme. Structural proteins are usually defective when one of the allelic products is nonfunctional;

Question 7

What is significant about enzymes of autosomal recessive inherited single gene disorders?

Answer 7

enzymes usually require both allelic products to be nonfunctional to produce a mutant phenotype:

Question 8

What is the aetiology of acquired disease?

Answer 8

Infections
Enviromental- chemical + physical
Nutritional

Question 9

What is a deficiency of vitamin C?

Answer 9

Scurvy

Question 10

What is a deficiency of vitamin D?

Answer 10

Rickets

Question 11

What is the aetiology of multifactorial disease?

Answer 11

A combination of genetic factors and environmental factors

Question 12

When does cell injury occur?

Answer 12

Occurs when cells are stressed so severely they are no longer able to adapt

Question 13

What are the two types of cell injury?

Answer 13

Reversible (non-lethal) and irreversible (death)

Question 14

What is the cellular response to stress?

Answer 14

Stress leads to an cell adaptation and if there is an inability to adapt this will lead to a cell injury

Question 15

What is the cellular response to severe cell injury?

Answer 15

Causes an irreversible injury which will lead to either necrosis or apoptosis

Question 16

What is the cellular response to mild cell injury?

Answer 16

Reversible injury where the normal cell will resume through homeostasis
Stress will lead to an adaption
An injury stimulus will cause another cell injury

Question 17

What happens in the cell during injury?

Answer 17

Mechanical Disruption of cells 
Insufficient energy 
Blockage of metabolic pathways
Failure of membrane pumps
Generation of free radicals 
Damage to DNA
Release of lysosomal contents

Question 18

What does damage to ATP lead to?

Answer 18

Loss of energy dependent cellular fucntions

Question 19

What does cell membrane damage lead to?

Answer 19

Mitochondrial failure -ATP
Lysosomes -required for enzymatic digestion of cellular components
Plasma membrane- loss of cellular contents

Question 20

Why is ATP depletion important?

Answer 20

tissues with low glycolytic activity eg neurons, cardiac muscle where ATP depletion is dependent on oxidative phosphorylation

Question 21

What causes early release of calcium into the cytosol?

Answer 21

Ischaemia and some toxins

Cytosolic free calcium levels are 10 fold lower than extracellular fluid and maintained by ATP dependent pumps

Question 22

What can lead to oxidative stress?

Answer 22

Reactive oxygen species (free radicals) accumulate when production exceeds the cells antioxidant defences

Question 23

What is the significance of the loss of the plasma membrane?

Answer 23

Maintain ionic balance between compartments occurs as a primary or secondary consequence of virtually all types of cell injury and particularly affects the mitochondria

Question 24

What are examples of reversible cell injury?

Answer 24

Reduced oxidative phosphorylation resulting in depletion of ATP energy stores
Cellular swelling caused by changes in ion concentrations and water influx.

Question 25

What two morphological examples of reversible cell injury?

Answer 25

Swelling of the cell (Hydropic change )
Fatty change (steatosis)

Question 26

What is hyopic change?

Answer 26

Impaired function of energy- dependent ion pumps in plasma membrane

Question 27

What is steatosis?

Answer 27

Deranged lipoprotein transport leads to accumulation of lipid in the cytoplasm of heptocytes

Question 28

What are causes of steatosis?

Answer 28

Alcohol and obesity

Question 29

Define necrosis?

Answer 29

Catastrophic cell death following injury accompanied by the release of potent mediators of inflammation

Question 30

Define apoptosis

Answer 30

A defined orderly sequence of intracellular events leading to cell death

Question 31

What are factors that cause necrosis?

Answer 31

Decreased oxygen
Infection
Toxins
Trauma

Question 32

What are the distinct patterns of necrosis?

Answer 32

Colliquative
Coagulative
Caseous

Question 33

What is the most commonest form of necrosis? and how is this viewed upon microscopy?

Answer 33

Coagulative

Peservation of the basic outline of the cells is seen until cells removed by phagocytosis

Question 34

Where is colliquative necrosis found?

Answer 34

Seen only brain

Question 35

What is caseous necrosis?

Answer 35

Cheese like

Dead tissue show no structure cell outlines not evident on microscopy

Question 36

What are features of apoptosis?

Answer 36

Energy dependent:active process
Cells break into fragments apoptotic bodies and express vitronectin
No inflammatory reaction

Question 37

What are caspases?

Answer 37

Intracellular proteases which play an important role

Question 38

What activates caspases?

Answer 38

Extrinsic pathway -signals from outside the cell

Intrinsic pathway-internal pathways such as DNA damage

Question 39

Why do we need apoptosis physiologically?

Answer 39

Eliminates cells no longer needed maintaining a steady number of various cell populations

Question 40

Why do we need apoptosis pathologically?

Answer 40

Eliminates cells that are injured beyond repair

Question 41

What are the stages of apoptosis?

Answer 41

Cell shrinkage 
Chromatin condensation 
Membrane Blebbing 
Nuclear Collapse 
Continued Blebbing 
Apoptotic Body formation 
Lysis of apoptotic bodies

Question 42

Learn differences between apoptosis and necrosis

Answer 42

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