Cellular Adaptations and Cellular Damage Flashcards
Define cell adaptation
Reversible changes in cells due to changes in environment (pathological or physiological) Changes can be in number, size or type of cell
What are the 3 types of cells in terms of proliferative capacity?
Labile cells: continuously divide in adult life e.g. skin
Stable cells: infrequently divide but can divide rapidly if needed e.g. bone
Permanent cells: Never divide in adult life e.g. brain tissue
What are the 4 types of cellular adaptation?
Hypertrophy
Hyperplasia
Metaplasia
Atrophy
Define hyperplasia
What type of cells does this occur in?
Give some examples of tissues this can occur in
Increase in the number of cells within a tissue (labile or stable cells)
Reversible
- Hormonal= endometrium during menstrual cycle
- Compensatory= e.g. liver after partial hepatectomy
- Pathological= e.g. chronic irritation, excessive growth factor stimulation
Define hypertrophy
Increase in cell size (increase in size of structural proteins)
Can occur in any cells, common in:
- Permanent cells experiencing increased demand e.g.
- Skeletal muscle
- Uterine muscle in pregnancy
- Pathological: e.g. cardiac muscle
Define atrophy
- Reduction in cell size due to a loss of cell substance
- Involves self digestion of organelles (autophagy)
- e.g. ageing (brain), reduced workload, reduced blood supply
Define metaplasia
- Reversible change of one mature adult cell type to another
- Adaptive response
- Usually involves epithelium
E.g.
- Normal: Glandular to squamous epithelium in development of cervix
- Pathological: oesophageal mucosa squamous to columnar epithelium in reflux oesophagitis (Barrett’s oesophagus)
What are the types of abnormal cell growth?
Dysplasia
Neoplasia
Define agenesis
Failure of differentiation into organ-specific tissue
Define dysplasia
Premalignant condition, occurs in labile tissues
- Increased cell growth
- Affects epithelia (e.g. cervix, bladder, stomach)
- Altered differentiation
- Cells mutate in a way that is not recognised by the cells’ regulatory mechanisms
- Can acquire new mutations and become cancerous
- Type of neoplasia
Define neoplasia
Abnormal growth of cells that persists after the stimulus has been removed
Cell growth escapes normal regulatory mechanisms:
- Benign
- Malignant- invasion and metastases
Define cell injury
Stimulus affecting cell has overwhelmed its capacity to adapt
What can cause cell injury and/or death?
- Hypoxia
- Physical agents (e.g. trauma, heat, cold)
- Chemicals and drugs
- Infection
- Immune reactions (e.g. autoimmune, hyper-sensitivity or immunodeficient)
- Genetic derangements
- Nutritional imbalances (excess of insufficiency)
Why is ischaemia worse than hypoxia?
Hypoxia is oxygen deprivation (e.g altitude, anaemia)
Ischaemia is oxygen deprivation as well as lack of nutrients; build up of toxins occurs so cell injury is quicker and more severe (e.g. blockage of blood vessel)
What are the most common mechanisms of chemical injury to cells?
- Damage to the osmotic environment
- Biochemical cell reactions, e.g. lack of ATP
- Damage to integrity of cell membrane
What is Marasmus?
Inadequate calorie intake resulting of metabolism of body tissues, e.g. skeletal muscle
What is Kwashiorkor?
Adequate calorie intake but inadequate protein intake
- protein stores in liver depleted
- Liver’s ability to produce proteins is lost
- e.g. albumin, loss of oncotic pressure of blood
How does depletion of ATP cause damage to cells?
Loss of oxidative phosphorylation in mitochondria =
- Loss of Na+ pump→influx of Na+ & Ca2+, efflux of K+→cellular swelling
- Anaerobic glycolysis →acidosis
- Detachment of ribosomes→decreased protein synthesis
What can be caused by damage to the mitochondria?
Depletion of ATP
Generation of reactive oxygen species
Damage to mitochondrial membrane = membrane proteins released into cytosol causing cell apoptosis
How can increased Ca2+ concentrations in cell cytoplasm cause damage?
Activates enzymes which break down cell membrane
Damage to DNA
ATP depletion
Can directly activate enzymes responsible for apoptosis
What causes free radical production?
Absorption of radiant energy (e.g. UV light)
Enzymatic metabolism of chemicals (e.g. carbon tetrachloride)
Inflammation
How are free radicals removed?
Antioxidants
Storage proteins (e.g. ferritin, transferrin)
Enzymes (e.g. catalase)
How do free radicals cause damage?
Direct DNA strand damage
Interaction with proteins
Membrane lipid peroxidation→autocatalytic chain reaction
What are the 2 types of cell death?
Necrosis
- Always abnormal, pathological
- Unregulated
- Enzymatic cell digestion→ contents leak out
Apoptosis
- Normal (pathological or physiological)
- Internally controlled
- Nuclear dissolution
What are the different types of necrosis?
-
Coagulative:
- Ischaemia
- Cells die but substructure of tissue is maintained (e.g. kidney)
- No enzymatic digestion of cells
-
Liquefactive:
- Dead tissue replaced by liquid material
- Enzymatic digestion of cells
- Usually caused by inflammation, not usually ischaemic except in brain
- Caseous: e.g. tuberculosis
- Fat: Enzymes access and digest fat cells, e.g. pancreatitis
-
Infarction: Ischaemic necrosis due to reduced blood supply
- White: blockage of arterial supply
- Red: blockage of venous supply
Give some examples of physiological and pathological apoptosis
Physiological:
- Embyrogenesis
- Involution of hormone dependent tissue
- Cell loss in proliferative cell populations
- Elimination of potentially harmful lymphocytes
- Cells no longer required
Pathological:
- Cells with DNA damage, or endoplasmic reticulum stress
- Pathological atrophy if a duct is obstructed
- Virus infected cells
How does apoptosis occur?
Imbalance between anti-apoptotic and pro-apoptotic molecules in the cell
- Activation of caspases
- DNA and protein breakdown
- Recognition by macrophages
What disorders can be caused by dysregulated apoptosis?
Defective apoptosis with increased survival:
- Autoimmune
- Neoplastic
Defective apoptosis with decreased survival:
- Ischaemic injury
- Death of virus infected cells
