PMI03-2009 Flashcards
What affects a cell’s response to injury?
Type, duration and severity of stimulus
Cell type, status, capability, genetic makeup
What are the two ways in which a cell can respond to injury?
Adaptation
Death
What is a labile cell? Give an example.
Continually cycling/replicating
Keratinocytes
What is a stable cell? Give an example.
Cell that has temporarily exited the cell cycle (G0), “quiescent”
Liver cells
What is a permanent cell? Give an example.
Terminally differentiated cell
Neurons/heart cells/RBCs/skeletal muscle cells
What type of cell is likely to be more inclined to adapt to injury/stimuli?
Labile cell
What type of cell is likely to be more inclined to die in response to injury/stimuli?
Permanent cell
What is hyperplasia?
Increase in the number of cells within a tissue or organ without an associated increase in size of cells
When does hyperplasia occur in response to a stimulus?
When cells are able to divide (labile and stable cells)
Give a physiological example of hyperplasia in response to a stimulus.
Hyperplasia of glandular tissue in female breast during puberty (hormonal)
Give a pathological example of hyperplasia in response to a stimulus.
Hyperplasia of prostate during hormonal imbalance
Chronic hyperplastic candidiasis (fungal infection)
What is hypertrophy?
Increase in size of cells without increasing in number
When does hypertrophy occur in response to a stimulus?
When cells are not able to divide (permanent cells)
Give a physiological example of hypertrophy in response to a stimulus.
Increase in muscle bulk following exercise
Give a pathological example of hypertrophy in response to a stimulus.
Left cardiac ventricle hypertrophy in heart failure (hypertension increases load)
Why are hyperplasia and hypertrophy often seen together?
They are responses to similar stimuli
What is atrophy?
Reduction in the size of an organ as a result of a reduction in the size and number of cells
Give a physiological example of atrophy in response to a stimulus.
Changes in vaginal epithelium due to menopause (hormonal)
Give a pathological example of atrophy in response to a stimulus.
Atrophic buccal epithelium in Lichen Planus (lymphoid infiltration)
What may cause atrophy?
Mutations
Poor nourishment
Loss of hormonal support
Loss of nerve supply to organ
Lack of organ/muscle use
What is metaplasia?
Change from one differentiated cell type to another
Why does metaplasia occur?
To better equip the affected area against the insult
Give an example of metaplasia relating to the oral cavity.
Squamous metaplasia of glandular epithelium
Trauma causes metaplasia of duct cells of minor salivary glands (cuboidal to squamous)
What is dysplasia?
Disordered stratification and disordered maturation
What causes dysplasia?
Persistent noxious agents (eg carcinogens)
What can metaplasia progress to after sufficient length and exposure of a stimulus?
Dysplasia
What is reversible injury?
Cell changes that can be restored to normalcy with removal of stimulus
What is irreversible injury?
Stressors exceed the capacity of the cell to adapt
Permanent changes lead to cell death
What are the possible causative agents of cell adaptation or death?
Physical = trauma, thermal, radiation
Chemical = carbon monoxide, cigarette smoke, ethanol
Infectious = toxins, metabolic products, lysis, DNA damage, viruses
Oxygen deprivation = hypoxia, ischaemia, anaemia
Immunologic = complement activation, cell-mediated cytotoxicity, autoimmunity, hypersensitivity
Genetic abnormality
Nutritional deficiency
What are the possible mechanisms of cell injury?
Disruption of metabolism
- ATP depletion
- mitochondrial damage
Nutrient/growth factor deprivation
Free radical/ROS formation
DNA damage by ROS
Membrane disruption
Inflammatory cell action
What stimuli may cause ROS formation?
Ionising radiation
Inflammation
Some drugs and metals
What can ROS damage in a cell?
Membranes
DNA
Other molecules in metabolic pathways
What are the two types of cell death?
Apoptosis
Necrosis
What are the five types of cell adaptation?
Hyperplasia
Hypertrophy
Atrophy
Metaplasia
Dysplasia
Describe necrosis.
Membrane damage is irreparable and leads to swelling
Pathological and not energy-dependent
Initial increased eosinophilia due to degradation of cytoplasmic RNA
Later loss of nuclear definition (karyolysis) as it loses its basophilia
Bursting of cell elicits an inflammatory response
What are the steps leading up to karyolysis?
Pyknosis = condensation of nucleus so it appears darker
Karyorrhexis = fragmentation
Karyolysis
What are the different types of necrosis?
Coagulative
Liquefactive
Caseous
Fat
Gangrene
Fibrinoid
What is coagulative necrosis?
Most common form of necrosis
Structural pattern of necrotic tissue is maintained
Commonly caused by ischaemia and infarction
What is a common cause of coagulative necrosis?
Ischaemia and infarction
Give an example of where you might see coagulative necrosis?
Renal cortex - tubular structure remains
What is liquefactive necrosis?
Changes in organ results in a collection of liquid, viscous material and no cell outlines visible
Common with CNS tissue necrosis
Formation of pus on infection
What is caseous necrosis?
Necrotic tissue resembles soft cheese microscopically - soft, white, proteinaceous dead cell mass
Typical for certain types of granulomatous inflammation, esp TB
What disease typically displays caseous necrosis?
Tuberculosis
What is fat necrosis?
Action of lipases on fatty tissues produces grossly visible, chalky white areas
Seen in breast, omentum and pancreatitis
What is gangrenous necrosis?
Necrosis of an appendage usually due to ischaemia
Green-black = due to breakdown of Hb
Coagulative or liquefactive necrosis can occur depending on secondary infection
What is fibrinoid necrosis?
Connective tissues and arterial walls are infiltrated by strongly eosinophilic hyaline material that shows characteristics of fibrin
Describe apoptosis.
Regulated and targeted programmed cell death
Energy-dependent
Can be physiological or pathological
Cell shrinkage and does not elicit inflammatory response
What may trigger apoptosis?
DNA damage
Protein misfolding
Viral infection
What are the two pathways of apoptosis?
Extrinsic/death receptor-mediated pathway
Intrinsic/mitochondrial-dependent pathway
Describe the extrinsic/death receptor-mediated pathway.
Death/Fas ligand binds death/Fas receptor
Activates cascade of initiator caspases which will activated executioner caspases
Eventual activation of caspase 8 which causes activation of caspase 3
Leads to dismantling of DNA and cytoskeletal proteins
Describe the intrinsic/mitochondrial-dependent pathway.
Cytochrome C release after DNA damage causes downstream activation of caspase 9 which activates caspase 3
What are the morphological state of apoptosis?
Early stages characterised by shrinkage of nucleus and cytoplasm (reversible)
Progresses to formation of membrane-bound bodies containing organelles (apoptotic bodies)
Apoptotic bodies phagocytosed by inflammatory cells
Give an example of physiological apoptosis.
Lymph node germinal centres - B cell negative selection
Give an example of pathological apoptosis.
Atrophy in oral Lichen Planus is caused by apoptosis
Induced by lymphocytes within the lamina propria
Contrast necrosis and apoptosis.
Necrosis
- pathological
- involves groups of cells
- swelling of cell
- not energy-dependent
- elicits an inflammatory response
Apoptosis
- physiological or pathological
- involves individual cells
- shrinking of cell
- energy-dependent
- no inflammation elicited
What is autophagy?
A response to cell stress
Ability of cell to recycle its own contents
Describe the process of autophagy.
Starts with formation of isolation membrane
Isolation membrane elongates to isolate off subcellular organelles = autophagosome
Autophagosome merges with lysosomes
Degradation and deconstruction of organelles, ready to be reused
