(Mine) Cellular Pathology Flashcards
Pathological stimuli brings about what changes?
Cell stress response.
Increased output of normal structural proteins and increased output of proteins with organising and protective functions.
Severe stimuli can lead to death.
What is the function of chaperones?
Correct protein folding and can remove old or misfolded proteins through the ubiquitin-protease pathway.
Explain the ubiquitin-protease pathway
- Activated ubiquitin linked to damaged protein
- Ubiquitinated protein recognised by protease
- Abnormal protein destroyed
- Ubiquitin recycled
Define:
Atrophy
Hypertrophy
Involution
Hyperplasia
Metaplasia
Atrophy - reduction in size of cells
Hypertrophy - increase in size of cells
Involution - decrease in cell numbers
Hyperplasia - increase in cell numbers
Hyperplasia - stable change to another cell type
How is atrophy/involution achieved?
By increased catabolism of structural proteins by autophagy.
- occurs due to lack of nutrients
- degradation of cytoplasmic components within lysosomes
Examples of physiological and pathological atrophy/involution
Physiological - thyroid gland after pregnancy, skeletal muscle in old age
Pathological - disuse atrophy (immobilised limb), denervation atrophy (damage to axons), ischaemic atrophy (gradual reduction in blood supply)
How would these cells adapt to deal with stress?
1. Bronchial columnar cells to cigarette smoke
2. Transitional cells of bladder to bladder stone
3. Fibrocollagenous tissue to abnormal use
4. Oesophageal squamous cells to gastric reflux
- Squamous cells
- Squamous cells
- Bone deposition
- Columnar cells
Metaplasia -> Dysplasia -> Tumour
What are primary targets for damaging stimuli?
Cell membrane, mitochondria, protein synthesis/packaging machinery, cellular DNA
How does cell death occur?
When damage threshold is passed, either:
- decrease in oxygen and nutrients
- by toxins e.g. cyanide
What causes primary cell membrane and mitochondria injury?
Cell membrane- O2 free radicals, immune mediated damage, direct actions of bacterial toxins
Mitochondria - all types of cell injury
What are the effects of a lack of ATP?
- Deficiency of oxygen leads to the failure of many metabolic processes that require energy
- Failure of Ca2+ pumps can cause severe damage
- Uncontrolled entry of Ca2+ into the cell
- Uncontrolled enzyme activation
What are oxygen free radicals?
Metabolic intermediates of toxins and drugs. Chemical species with a single unpaired electron in an outer orbit - unstable and react with inorganic/organic material
How do reactive oxygen metabolites cause cell damage?
- Increase permeability in the membrane lipid
- Critical protein damage e.g. Na/K ATPase pumps
- DNA fragmentation - possible role in malignancy
- O2 free radicals are scavenged by protective antioxidant systems
What causes necrosis due to disintegration of cellular structure? Explain
Activation of lysosomal enzymes. Lysosomal enzymes contribute to the breakdown of organelles, leading to uncontrolled cellular lysis. Outcome is cell contents leak into extracellular space, triggering inflammation and damage to the surrounding tissue.
Explain apoptosis necrosis (necroptosis)
Is the normal process. Removes unnecessary cells but can also remove damaged cells. Plasma membrane intact with no leakage of contents and no activation of inflammatory response.