Week 1 - Lecture 2b - Cellular Adaptation and Response to Stress, Injury and Death

Question 1

name three causes of cell stress and injury

Answer 1

deficiency
intoxication
trauma

Question 2

Define deficiency

Answer 2

lack of substance necessary to the cell

• variety of specific chemicals
• energy supply

Question 3

What can cause deficiency

Answer 3

nutritional deficiency
genetic disease
infection

Question 4

Define intoxication

Answer 4

the presence of a substance that interferes with cell function

Question 5

Origin intoxications

Answer 5

outside the cell - external : exogenous : biological or non-biological
Inside of the cell - internal : endogenous : biological

Question 6

examples of external biological intoxication

Answer 6

produced by agents of infection

- bacteria, fungi

Question 7

examples of external non-biological intoxication

Answer 7

injurious chemicals

• inhalation, swallowing
• need to achieve a dose high enough to cause injury
• • therapeutic drugs - effective at prescribed level. can be fatal at high doses (barbiturates)

Question 8

endogenous intoxication

Answer 8

genetic defect

abnormal accumulation

Question 9

Define trauma

Answer 9

physical injury or damage resulting in loss of the cell’s structural integrity

some cases instant loss as a result of great damage
some cases physical damage arises gradually

Question 10

Mechanisms of cell injury

Answer 10

direct (for example thermal injury)
indirect : 3 major mechanisms
- hypoxic cell injury 
-free radical injury 
- impaired calcium homeostasis

Question 11

define hypoxia

Answer 11

cellular deprivation of oxygen

oxygen supply via blood is compromised

Question 12

hypoxic injury

Answer 12

1 : result of ischemia : interruption of blood supply;to tissue

• rapid interruption is severe, metabolic needs are high
• angina pectoris, stroke, cerebral ischemia, transient ischemic attack (TIA)

2. result of other conditions
   -poor oxygen levels (anemia)
   -imparied oxygenation (lung disease)
   Toxic agents (CO, H2S, cyanide)

Question 13

define anoxia

Answer 13

complete lack of oxygen in blood (absolute deprivation

Question 14

8 steps for an ischemic injury

Answer 14

1. blood flow compromised
2. cell switch to anaerobic metabolism to maintain ATP level
3. By-product is lactic acid (LA)
4. Accumulating LA disrupts mitochondria
5. decreasing ATP production results in dysfunction of membrane pumps
6. Excessive sodium influx (Na/K ATP pump failed)
7. Increased osmotic pressure (sodium is followed by water)
8. Cell swell, waste products continue to accumulate
   - 1. if hypoxia ceased : cell will not die
   - 2. if not : cell dies

Question 15

Re-perfusion injuries

Answer 15

‘secondary injury’

• re-perfusion of the tissue leads to further damage
• membrane pumps are still impaired

Question 16

Free radicals and reactive oxygen species (ROS)

Answer 16

electrically uncharged atom or group of atoms having an unpaired electron that cause damage via :
:lipid peroxidation

Question 17

Impaired calcium homeostasis

Answer 17

Ca2+ is an important second messenger and cytosolic signal for many cell responses

Intracellular Ca2+ concentration is low
– some Ca2+ is stored

Calcium activates enzymes in the cell

if Ca2+ homeostasis impaired

• intracellular Ca2+ increases
• mitochondria damaged, reduced ATP production
• intracellular destructive enzymes are activated
• cell membrane and cytoskeleton destroyed

Question 18

Cellular adaptation and response to stress and injury

Answer 18

1. cells have a variety of mechanisms to cope with stress

2. they can live through unfavourable conditions

Question 19

5 processes of adaptation

Answer 19

atrophy
hypertrophy 
hyperplasia
metaplasia
dysplasia

Question 20

What is atrophy

Answer 20

decrease in the size of a cell

due to

• decrease in functional demand (muscular atrophy due to immobilised in cast)
• decrease oxygen supply
• removal of signals (neural : poliomyelitis / growth hormone: involution [decreased size, tissue and organ])
• nutritional deprivation
• ageing

Question 21

loss of function associated with atrophic cell and tissue changes

Answer 21

spinal muscular atrophy

• degeneration of motor neurone of the spinal cord
• genetic condition
• resulting in weakness of voluntary muscles

Question 22

Hypertrophy definition

Answer 22

increase in cell size

Question 23

hypertrophy cause

Answer 23

increase in trophic (growth) signals
- signals increase > sex hormones
-increased sex hormones > hypertrophied reproductive cells during puberty
-during pregnancy hypertrophied breast cells > breast milk
Increase in demand
- strength building exercise

Question 24

What is hyperplasia

Answer 24

increase in number of cells

Question 25

what causes hyperplasia

Answer 25

increase in trophic (growth) signals increase in demand - some of the same conditions as for hypertrophy -often appear together

Question 26

hyperplastic adaptation

Answer 26

uterus responds to increased hormone levels during menstrual cycle

Question 27

Adaptation to hormonal signals

Answer 27

dynamic process one cell or tissue can undergo series of adaptation response - ductal tissue of the breast A: puberty - hyperplastic changes B: pregnancy - hypertrophic change : to support production and delivery of milk C: menopause - atrophic changes

Question 28

What is metaplasia

Answer 28

changing of one cell type to another cells are fully differentiated cells adapt to chronic or persistent stressor if stimulus removed, cells revert back to their original type most common type : epithelial tissue

Question 29

example of metaplasia

Answer 29

squamous metaplasia in bronchial tubes etiology - stressor : cigarette smoke - Ciliated columnar cells turn to squamous epithelium - when stressor is removed cells often return to normal - if stressor persist: cell may develop changes that lead to pathologic changes

Question 30

What is dysplasia

Answer 30

Change in cell size, shape, uniformity, arrangement and structure - response to chronic and persistent stressor -likely to resolve after stressor is removed Cells are not cancerous, but can progress to cancer

Question 31

Dysplasia aetiology

Answer 31

abnormal differentiation - DNA may be reproduced with mutations -these mutations are repeated as cells divide and proliferate Larger changes to chromosomes may be evident A: normal cells, large squamous cells with small nuclei B: mild dysplasia, increased nucleus size, darkened colour C: severe dysplasia, markedly enlarged nucleus with abnormal chromatin

Question 32

Example of dysplasia

Answer 32

bronchopulmonary dysplasia bronchial and alveolar tissue of the lungs -become thickened -reducing ability to take air into lungs and oxygenate tissue -reducing ability to excrete waste products and CO2 Etiology : multifactorial - immature lung tissue is susceptible damage - premature infants require mechanical ventilation to treat respiratory distress syndrome - -over distend airways and airspaces in infant - -stressor prompt cellular alterations - -chronic, irreversible tissue change

Question 33

Cellular death is caused how

Answer 33

if the stressor is too great | or the stressor is too long

Question 34

what are the two types of cellular death

Answer 34

apoptosis | necrosis

Question 35

What is apoptosis

Answer 35

adaptive response : involves a reduction in cell numbers by a process of self destruction programmed cellular death prompted by highly-controlled signals cell death does not result in release of intracellular fluids to surrounding microenvironment

Question 36

What are the reasons for apoptosis

Answer 36

development of limbs day to day removal of unrequited cells (eg. immune system, uterus during the menstrual cycle) damaged genetic material, maturation cells undergo apoptosis to prevent transformation into a cancer cell can be physiological or pathological

Question 37

examples of when apoptosis is used wrong

Answer 37

webbing hands into digits during the 7th week doesn't occur most cancers, Parkinson's, alzeimer's - does not take place in presence of correct stimuli

Question 38

Apoptosis cycle

Answer 38

activation of internal signals (eg. severe genetic damage) or external signals (eg. immune cells) activate a cascade of intracellular reactions cell shrinks, membrane blebs DNA and nucleus fragments whole cell fragments into apoptotic bodies and phagocytosed

Question 39

What is necrosis

Answer 39

disorderly process associated with inflammation | always pathological, related to cell injury

Question 40

11 steps of necrosis

Answer 40

1. poor ATP production 2. dysfunction of membrane 3. excessive sodium ion influx 4. cause strong osmotic pressure 5. draws water into cell 6. calcium ions are released from cytoplasmic stores 7. intracellular enzymes are activated 8. these enzymes impair mitochondria and damage membrane 9. Blebs (blisters) are formed 10. Toxic chemicals accumulate 11. eventually cell membrane rupture and inflammation follows

Question 41

5 types of necrosis

Answer 41

``` coagulative liquefactive caseous fat gangrenous ```

Question 42

coagulative necrosis

Answer 42

kidneys, heart, adrenal glands caused by hypoxia protein denaturation - albumin change from transparent state

Question 43

liquefactive necrosis

Answer 43

irreversible ischaemic injury to nerve cells in the brain | brain cells have high levels of digestive enzymes, and the brain has small amounts of connective tissue

Question 44

caseous necrosis

Answer 44

tuberculosis pulmonary infection | combination of coagulative and liquefactive necrosis

Question 45

Fat necrosis

Answer 45

adipose tissue | action of lipases : triglycerides > free fatty acids

Question 46

gangrenous necrosis

Answer 46

death of tissue from severe hypoxic injury - common due to blockage of arteries - bacterial infraction dry gangrene -skin dries, shrinks, becomes brown, black wet gangrene - usually in internal organs - neurophils (main WBC) invade the site - liquefactive necrosis - site cold, swollen, black - if it becomes systemic: death can ensue