Lecture: Pathology 2: How the cell responds to injury Flashcards
How does tissue grow?
Increase in cell size or number by synthesis of new components. Different tissues show different proliferative ability.
What does the term multiplicative mean?
Increase in cell number by mitotic division
What does the term auxetic mean?
Increase in cell size
What does the term accretionary mean?
Increase in extracellular tissue
What is the role of cell turnover?
Cell turnover permits maintenance of continuously growing tissues (e.g. skin, intestinal mucosa) and healing (injury, disease).
What are labile cells?
Cells that continuously proliferate, have a short lifespan and a rapid turnover time
What are examples of labile cells?
White blood cells and many epithelial cells
What are stable cells (facultative dividers)?
Cells that have good regenerative ability but would normally have a low cell turnover
What are examples of stable cells?
Quiescent tissues e.g. hepatocytes
What are permanent cells?
Cells that have very little or no regenerative ability
What are examples of permanent cells?
Terminally differentiated cells, eg. keratinocytes, neurons, cardiac and skeletal muscle, and red blood cells.
How do cells acquire specialised functions?
Cells acquire a specialised function and this is a results of selective expression of genes. Disease replicates this process e.g. in neoplasia.
What determines severity of cell injury?
Cell injury depends on the duration and severity of the stimulus. Cell injury occurs if cells are so severely stressed that they can no longer adapt.
What are the 3 pathways following cell injury?
- Adapt
- Reversible cell injury (return to normal)
- Irreversible cell injury (necrosis or apoptosis)
What is hypertrophy?
Increase in cell size owing to increase in structural components; only adaptive response available to permanent cells (e.g. cardiac muscle cells).
What are examples of physiological hypertrophy?
- Hypertrophy of skeletal muscle through training
* Uterine hypertrophy owing to hormone stimulation
What are examples of pathophysiological hypertrophy?
- Cardiac hypertrophy owing to hypertension or valvular disease
- Bladder hypertrophy owing to prostatic enlargement
How does pathological hyperplasia differ from neoplasia?
Pathological hyperplasia is distinct from neoplasia but increased cell turnover increases the risk of genetic aberrations/mutations and thus neoplasia.
What is hyperplasia?
Increase in cell number that requires cells that are able to divide (labile or stable cells).
What triggers hyperplasia?
Hyperplasia is triggered by growth factor activation and stem cell activation.
What are examples of pathophysiological hyperplasia?
- Endometrial hyperplasia owing to excess oestrogen
- Prostatic hyperplasia owing to excess androgens
- Virus induced hyperplasia in warts (HPV)
What are examples of physiological hyperplasia?
- Breast development and breast feeding
* Partial liver resection or bone marrow hyperplasia in bleeding
What is atrophy?
Reduction of the size of cells (and cell organelles) and reduction of cell numbers (apoptosis).
What triggers atrophy?
Triggered by degradation of cellular organelles/proteins by ubiquitin-proteasome pathways.
What are examples of physiological atrophy?
- Atrophy of uterus after parturition
* Atrophy of developmental structures
What are examples of pathophysiological atrophy?
- Vascular atrophy of the brain
* Malnutrition / starvation / marasmus
What is metaplasia?
Reversible change where one differentiated cell type/tissue is replaced by another differentiated cell type/tissue in response to environmental change. Usually seen in epithelium but possible in mesenchymal tissues.
What triggers metaplasia?
Triggered by stem cell differentiation and/or colonization by differentiated cells from nearby tissues.
What are examples of pathophysiological metaplasia?
- Metaplasia from bronchial ciliated columnar epithelium to stratified squamous epithelium in response to smoking.
- Metaplasia from oesophageal stratified squamous epithelium to columnar epithelium in response to acid reflux (Barrett’s oesophagus).
What are examples of physiological metaplasia?
Metaplasia of cervical simple columnar epithelium to stratified squamous epithelium in response to acidic vaginal environment.
What is reversible cell injury?
Reversible cell injury results in morphological and cellular changes, however restoration of homeostasis can be achieved when cellular stress is removed.
What is apoptosis?
Programmed cell death that does not result in inflammation as cell membrane remains intact but is altered. Normal, however, highly elevated in disease.
What is necrosis?
Cell lysis and ingestion by immune cells leading to an immunological response.
What are the 4 main characteristics of irreversible cell injury?
- Lysosome rupture and autodigestion
- Denaturation of proteins
- Membranes rupture
- Nuclear changes
How can irreversible cell damage be detected?
Leakage of cellular components from damaged cells into the blood allows for detection of injured tissues
What is necroptosis?
Cell death which shows both necrosis and apoptosis features
What is pyroptosis?
Apoptosis with fever and IL-1 signalling
How is apoptosis activated?
Activation of intracellular caspase enzymes to degrade DNA and proteins which allows for cell membrane to remain in tact but attract phagocytes to degrade cell without triggering immune response.
Caspase activated by death receptors and mitochondria-mediated receptors.
Examples of physiological apoptosis
Elimination of self-reactive / autoimmune lymphocytes
Programmed apoptosis of inflammatory cells at the end of the inflammatory response
Examples of pathophysiological apoptosis
DNA damage of any kind usually triggers apoptosis
Accumulation of abnormal proteins
What is ischemia?
Lack of blood flow to tissue and cells
What is ischaemia reperfusion injury?
Where restoration of blood flow, after a period of limited blood flow, exacerbates tissue damage.
What is autophagy?
Consumption of own tissue by lysosomal degradation
as a survival mechanism in nutrient deprivation
What regulates autophagy?
Regulated by autophagy genes
