Week 1 - Lecture 2b - Cellular Adaptation and Response to Stress, Injury and Death Flashcards
name three causes of cell stress and injury
deficiency
intoxication
trauma
Define deficiency
lack of substance necessary to the cell
- variety of specific chemicals
- energy supply
What can cause deficiency
nutritional deficiency
genetic disease
infection
Define intoxication
the presence of a substance that interferes with cell function
Origin intoxications
outside the cell - external : exogenous : biological or non-biological
Inside of the cell - internal : endogenous : biological
examples of external biological intoxication
produced by agents of infection
- bacteria, fungi
examples of external non-biological intoxication
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)
endogenous intoxication
genetic defect
abnormal accumulation
Define trauma
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
Mechanisms of cell injury
direct (for example thermal injury) indirect : 3 major mechanisms - hypoxic cell injury -free radical injury - impaired calcium homeostasis
define hypoxia
cellular deprivation of oxygen
oxygen supply via blood is compromised
hypoxic injury
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)
- result of other conditions
-poor oxygen levels (anemia)
-imparied oxygenation (lung disease)
Toxic agents (CO, H2S, cyanide)
define anoxia
complete lack of oxygen in blood (absolute deprivation
8 steps for an ischemic injury
- blood flow compromised
- cell switch to anaerobic metabolism to maintain ATP level
- By-product is lactic acid (LA)
- Accumulating LA disrupts mitochondria
- decreasing ATP production results in dysfunction of membrane pumps
- Excessive sodium influx (Na/K ATP pump failed)
- Increased osmotic pressure (sodium is followed by water)
- Cell swell, waste products continue to accumulate
- 1. if hypoxia ceased : cell will not die
- 2. if not : cell dies
Re-perfusion injuries
‘secondary injury’
- re-perfusion of the tissue leads to further damage
- membrane pumps are still impaired
Free radicals and reactive oxygen species (ROS)
electrically uncharged atom or group of atoms having an unpaired electron that cause damage via :
:lipid peroxidation
Impaired calcium homeostasis
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
Cellular adaptation and response to stress and injury
- cells have a variety of mechanisms to cope with stress
2. they can live through unfavourable conditions
5 processes of adaptation
atrophy hypertrophy hyperplasia metaplasia dysplasia
What is atrophy
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
loss of function associated with atrophic cell and tissue changes
spinal muscular atrophy
- degeneration of motor neurone of the spinal cord
- genetic condition
- resulting in weakness of voluntary muscles
Hypertrophy definition
increase in cell size
hypertrophy cause
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
What is hyperplasia
increase in number of cells
what causes hyperplasia
increase in trophic (growth) signals
increase in demand
- some of the same conditions as for hypertrophy
-often appear together
hyperplastic adaptation
uterus responds to increased hormone levels during menstrual cycle
Adaptation to hormonal signals
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
What is metaplasia
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
example of metaplasia
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
What is dysplasia
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
Dysplasia aetiology
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
Example of dysplasia
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
Cellular death is caused how
if the stressor is too great
or the stressor is too long
what are the two types of cellular death
apoptosis
necrosis
What is apoptosis
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
What are the reasons for apoptosis
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
examples of when apoptosis is used wrong
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
Apoptosis cycle
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
What is necrosis
disorderly process associated with inflammation
always pathological, related to cell injury
11 steps of necrosis
- poor ATP production
- dysfunction of membrane
- excessive sodium ion influx
- cause strong osmotic pressure
- draws water into cell
- calcium ions are released from cytoplasmic stores
- intracellular enzymes are activated
- these enzymes impair mitochondria and damage membrane
- Blebs (blisters) are formed
- Toxic chemicals accumulate
- eventually cell membrane rupture and inflammation follows
5 types of necrosis
coagulative liquefactive caseous fat gangrenous
coagulative necrosis
kidneys, heart, adrenal glands
caused by hypoxia
protein denaturation
- albumin change from transparent state
liquefactive necrosis
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
caseous necrosis
tuberculosis pulmonary infection
combination of coagulative and liquefactive necrosis
Fat necrosis
adipose tissue
action of lipases : triglycerides > free fatty acids
gangrenous necrosis
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
