Cellular response to injury Flashcards
Give the general overview of how cell response to injury works
noxious agent, mechanism of action, cell response, adaptation or death
How can one stimulus vary from another?
Type, duration and severity
What can cause cells vary their response?
Type, status (within the cell cycle), capability (to regnerate) and genetic makeup
What is the difference between these cells?
- labile
- stable
- permanent
Labile cells - continually in cell cycle, e.g. epidermis cells or oral epithelium
Stable cells - remain in G0, temporarily leaving cell cycle, can be recruited back in e.g liver cells
Permanent cells - undergone terminal differentiation, once lost there is no replacement of them, no stem cell compartment e.g. cardiac myocytes
What generally happens in a cell once injury has occured?
Functional change, structural change, signs & symptoms
What are the two types of stimuli?
Physiological and pathological
What are the 5 cells reponses commonly and explain each?
- Hyperplasia
- increase in number of cells without increase in cells size, occuring in cells able to cell divide - Hypertrophy
- increase in size of cells without an increase in cell number, happens in cell unable to divide - Atrophy
- reduction in size of an organ as a result in size or number of cell reduction - Metaplasia
- changing from one differentiated cell type to another - Dysplasia
- disordered stratification and maturation
- only reversible up to a point where sufficient genetic damage causes a dysplastic cell type to be permanently damaged
All reversible up to a point.
What are the 5 types of causative agents of cell damage?
- physical
- chemical
- infectious
- oxygen depriavtion
- immunologic
Explain the mechanism of cell injury
Disruption of metabolism - through ATP depletion, mitochondria are prone to damage after injury
Nutrient growth factor deprivation - could lead to disruption of metabolism, lack of endocrine/exocrine growth factor can cause further downstream metabolic mechanisms of cell injury
Free radicals - unpaired electron in outer orbit, they are highly damaging to adjacent molecules and can cause damage to proteins and carbohydrates, reactive oxygen species is a free radical type that under certain injurious conditions, these may accumulate within the cell and damage it. May result from ionising radiation, inflammation, drugs and metals. They cause DNA damage (triggers cell death).
Membrane disruption - free radicals target it both the plasma and organelle membranes, this causes disruption in cell homeostasis.
Increased intracellular calcium can harm cells.
Inflammation can cause cell death.
What are the two ways that cell death can occur?
Necrosis
- A point lies where membrane damage is no longer repairable. This membrane damage will lead to swelling. Swelling is associated with necrosis.
In early stages, necrosis is characterised by increased pink colour of the cell.
In early stages, you see condensation of the nucleus to give an increased basophillia (more red). This is pyknosis.
The condensation of the nucleus can be seen in necrosis and apoptosis. In necrosis, pyknosis is followed by karyorrhexis (degradation of the nuclei into smaller fragments).
Apoptosis
- Regulated and targeted programmed cell death
- Highly regulated and energy dependant
- Can be physiological (during elimination of high proliferating lymphocytes) or pathological (DNA damage, protein misfolding, viral infection).
- Caspase is a enzyme in cell death
What are the 3 types of necrosis?
- Coagulative (most common)
This is when the structural pattern of the necrotic tissue is maintained. - Liquefactive
Changes in the organ results in a collection of liquid viscous material.
No cell outlines can be seen. - Caseous
Typical in granulomiter inflammation. (covered a lot more later)
It is common in TB infection.
What are the two major pathways from which apoptosis can be induced?
Extrinsic (death receptor mediated pathway):
- Death ligand binds to a death receptor which upon activation causes the activation of downstream apoptosis intermediates known as caspases
- Caspases are brought about by the initiation of initiator caspases and through a cascade results in activation of executioner caspases
- Activation of caspase 8 results in activation of caspase 3 (executioner) which causes the initiation of apoptosis through the dismantling of DNA and cytoskeletal proteins
Intrinsic (mitochondrial dependant pathway):
- DNA damage causes release of cytochrome c
- Activation of caspase 9
- Activation of caspase 3
What are the physiological stages of apoptosis?
Shrinkage of nucleus and cytoplasms
Formation of membrane bound bodies containing organelles (apoptotic bodies).
Apoptotic bodies under phagocytosis by inflammatory cells.
Compare necrosis and apoptosis:
Apoptosis:
- cell shrinkage
- pathological or physiological
- individual cells
- energy dependent
- no inflammation
Necrosis:
- cell swelling
- pathological
- groups of cells
- not energy dependent
- inflammation
What is autophagy?
Response to cell stress aka in nutrient deprivation is the ability for the cell to recycle is own contents.
This is highly regulated and starts by the formation of the isolation membrane.
The isolation membrane then elongates to isolate off the organelles to form an autophagosome.
The autophagosome merges with lysosomes and the organelles components are they broken down which makes it ready for recycling.
