Cell Injury, Death and Degeneration Flashcards
What are the two mechanisms of cell death?
- Necrosis
- Apoptosis
What are the mechanisms of cell injury?
- Damage to mitochondria which disrupts aerobic respiration/ATP syntheses.
- Cell membrane disruption which causes disruption to ion concs.
- Damage to cytoplasm which disrupts enzyme and structural protein synthesis.
- Damage to nucleus which disrupts DNA maintenance and DNA damage.
- Oxidative stress which is caused by free radicles (lack of antioxidants can make damage more likely)
Describe features of reversible cell injury
- Can have ‘cloudy swelling’ which occurs due to osmotic disturbance (loss of energy dependant Na pump leads to Na influx and build up of intracellular metabolites). Cloudy swelling can cause cytoplasmic blebs, disruption of microvilli and swollen mitochondria.
- Can have ‘fatty change’ which is where a disruption of fatty acid metabolism can cause accumulation of lipid vacuoles in cytoplasm.
Describe features of cells death by necrosis vs apoptosis
Necrosis - Injury due to external stimuli, uncontrolled cell death which is always pathological. Cell contents leak from the breakdown of cell membrane stimulating an inflammatory response.
Apoptosis - Usually physiological but can be pathological. It is actively controlled and the cell contents do not leak due to the intact cell membrane so does not elicit an inflammatory response
What are the histological and nuclear changes seen in Necrosis?
Histological - Cell swelling, vacuolation and disruption of cell membranes and its organelles. Release of cell contents including enzymes which causes adjacent damage and acute inflammation.
Nuclear changes - Fading (Karyolysis), shrinkage (Pyknosis) and fragmentation (Karyorrhexis).
What are the morphological subtypes of necrosis
- Coagulative (Firm, tissue outline retained. Haemorrhagic or gangrenous),
- Colliquative (Tissue becomes liquid, seen in cerebral infarction),
- Caseous (Combination of coagulative and colliquative, appears cheese like, seen in TB).
- Fat (Due to action of lipases on fatty tissue)
What are some physiological examples of apoptosis?
- Embryogenesis (deletion of cell populations - prevents webbing of fingers)
- Hormone dependent involution (ovary, uterus).
- Deletion of inflammatory cells after inflammatory response
- Deletion of self reactive lymphocytes in thymus.
- Cell deletion in proliferating cell populations to maintain normal numbers.
What are some examples of pathological apoptosis?
- Viral infections (infected cells killed by cytotoxic T-lymphocytes),
- DNA damage,
- Hypoxia/ischaemia,
- Autoimmune disease,
- Graft vs Host Disease
Explain the morphology (process) of apoptosis
- Cell shrinkage with chromatin condensation (pyknosis) followed by karyorrhexis. Membranes of cell remain intact. Cytoplasmic blebs form and break off forming apoptotic blebs which are phagocytosed by macrophages
What are some endogenous and exogenous depositions?
Endogenous:
Intracellular - melanin, hemosiderin, bile.
Extracellular - Amyloid, fibrosis and calcium.
Exogenous (can be intracellular or extracellular): Tattoo pigment, carbon and asbestos
What is amyloid?
Localised or systemic accumulation of protein aggregates outside of cells. It is formed by abnormal folding of soluble protein fibrils into beta pleated sheets.
How is amyloid detected with microscopy?
With congo red stain. It shows pink and apple green under polarised light
What are the two main types of amyloid
AL amyloid: Immunoglobulin light chain produced by B-cell neoplasms (myeloma)
AA amyloid: Serum amyloid associated protein (acute phase protein) produced in the liver. It is produced in prolonged chronic inflammation (rheumatoid arthritis).
What are the possible clinical effects of amyloidosis?
- Renal impairment/failure,
- Heart failure,
- Dementia
Describe pathological calcium deposits
Can be:
- Dystrophic (Deposition in abnormal tissue but with normal serum calcium)
- Metastatic (Deposition in normal tissue but with raised serum calcium, often in CT of blood vessels, compromising tissue function)
