PATHOLOGY - Response to Injury I: Cellular and tissue responses Flashcards
Outline a brief overview of cell response
Noxious agent > mechanism of action >Cell response > Adaptation or cell death
What 3 factors of a stimulus may affect how a cell responds?
- type
- duration
- severity
What type of cells can be described as ‘stable’?
Hepatocytes
What type of cells can be described as ‘labile’?
Skin cells - epidermis
Or oral mucosa
What cells can be described as permanent cells?
CNS - axons
Or cardiac myocytes (once lost, cannot be replaced)
Following injury - describe the steps that then occurs in a cell (4)
- Molecular and genetic changes
- Functional change
- Structural change
- Signs and symptoms
Adaptive responses can be a result of which 2 types of stimulus?
Physiological
Pathological
Give an example of a hyperplastic condition that affects the oral cavity
Chronic hyperplastic candidosis
Gingival hyperplasia
What is hypertrophy of cells?
it is the increase in SIZE of cells without increase in NUMBER of cells
Why is it difficult to differentiate between hyperplasia and hypertrophy in a clinical setting?
Hyperplasia and hypertrophy usually occur side by side in response to the same stimulus
What is atrophy?
Decrease in size
Which oral condition could be described as causing pathological atrophy? Where would you see this?
Lichen planus
Buccal mucosa epithelium
What is metaplasia?
It is when one cell type differentiates into another
Outline the 5 ways cells may change in response to injury
- hyperplasia
- hypertrophy
- atrophy
- metaplasia
- dysplasia
What is dysplasia?
Abnormal cells - disordered stratification or maturation
Which cellular responses are considered reversible?
Hyperplasia
Hypertrophy
Metaplasia
Outline causative agents (5)
- Physical: trauma, thermal, radiation
- Chemical: CO, cigarette smoke, ethanol
- Infectious: toxins, metabolic products, lysis, DNA damage
- Oxygen deprivation: hypoxia, ischaemia
- Immunologic: complement activation, cell mediated cytotoxicity, autoimmune
How may metabolism be disrupted within a cell following injury?
- ATP depletion > frequently arises from hypoxia
- Mitochondria is a very sensitive organelle > prone to damage following injury, can arise from calcium influx or degeneration of reactive oxygen species. and susceptible to damage during hypoxic states
What may cause nutrient/growth factor deprivation occur in response to injury?
Ischemia, hypoxia
Lack of endocrine, exocrine or autocrine factor
what is a free radical species?
It is a chemical species that has a single, unpaired electron in its outer orbit
What does a free radical species do to a cell?
The unpaired electron can cause damage to adjacent molecules - including proteins, carbohydrates and amino acids (e.g. DNA)
What is ROS?
Reactive oxygen species
It is a type of free radical - product of normal cellular metabolism.
These may accumulate in the cell under certain conditions, and this is damaging to the cell.
What may cause excess free radicals?
Ionising radiation
Inflammation
Certain drugs
Certain metals
What are the main downstream targets of free radicals/ROS? (2)
DNA - potent trigger for cell death (e.g. apoptosis)
Membrane - plasma, mitochondrial or lysosomal membranes. Important in cell homeostasis. Can also be disrupted by increased levels of intracellular calcium.
Although poorly defined, at which point is it thought that a cell is set on a path of death?
Membrane damage no longer reparable
What morphological observation characterises necrosis?
Swelling mainly
Cells can look pinkier under microscope
What is thought to proceed karyolysis?
Pyknosis > karyorrhexis > Karyolysis
What is pyknosis?
It is where the nucleus (chromatin) is condensed - this is irreversible.
Can be seen in necrosis and apoptosis
What is karyorrhexis?
Destructive fragmentation of nucleus of cell whereby its chromatin is distributed irregularly throughout the cytoplasm
What is karyolysis?
Dissolution and disintegration of cell nucleus
What is the most common type of necrosis?
Coagulative necrosis
Name 2 common causes of coagulative necrosis
Ischemia and infarction
What type of necrosis results in a collection of liquid, viscous material?
Liquefactive necrosis
No cell outlines discernible
Common in CNS tissue e.g. Brain or bacterial of fungal infection with formation of pus
Why is caseous necrosis called caseous necrosis?
Because it resembles soft cheese macroscopically
Where is caseous necrosis most common?
TB infections
granulomatous
What is apoptosis? (4)
Regulated
Targeted
Programmed cell death
Energy-dependent
Outline the death receptor-mediated extrinsic pathway for apoptosis (4)
- Death ligand binds to death receptor
- Activates caspase 8
- …this downstream activates caspase 3 (executioner caspase)
- causes execution of apoptosis through dismantling of DNA and cytoskeletal proteins
Outline the mitochondrial-dependent intrinsic pathway for apoptosis (5).
When does this occur?
Brought about in circumstances of DNA damage.
- DNA is damaged
- Cytochrome C is released in response
- This downstream activates caspase 9
- This activates caspase 3 (executioner caspase)
- causes execution of apoptosis through dismantling of DNA and cytoskeletal proteins
What is an early morphological sign of apoptosis?
Shrinkage of the nucleus and cytoplasm
What stain can be used to show activated caspase 3?
Immunohistochemistry - shows as a brown colour
Is necrosis pathological or physiological?
Pathological
Is apoptosis pathological or physiological?
Can be either
Does necrosis involve groups of cells or individual cells?
Groups
Does apoptosis involve groups of cells or individual cells?
Individual
Which morphological feature is characteristic of necrosis?
Cell swelling
Which morphological feature is characteristic of apoptosis?
Cell shrinkage
Which is energy dependent - necrosis or apoptosis?
Apoptosis
Which elicits an inflammatory response - necrosis or apoptosis?
Necrosis
although apoptosis may be a RESULT of inflammation, it does not elicit this itself
What is autophagy?
Consumption of body’s own tissue as a metabolic process occurring in starvation/nutrient deprivation and certain diseases.
Recycle its own contents - highly regulated
Outline the steps involved in autophagy (3)
- isolation membrane develops and elongates around the subcellular organelles - forms autophagosome
- autophagosome binds with lysosome
- lysosomal contents begins to degrade and deconstruct the organelles into components ready for recycling
