L3- Cell injury Flashcards
Increased cellular activity
Hyperplasia
Hypertrophy
Decreased cellular activity
Atrophy
Change in cell morphology
Metaplasia
reversible replacement of one differentiated cell type with another differentiated cell type.
Aetiology of cell injury
Oxygen availability Physical trauma Chemical agents Infectious organisms Irradiation
Others:
- Immunological
- Lack of essential nutrients/vitamin
- Genetic disorders
- Ageing
Affects of Oxygen unavailability
Hypoxia and anoxia
-reduction or loss respectively of oxygen delivered to cells, often caused by ischaemia
Hypoxia = lack of oxygen Anoxia = absence of oxygen Ischaemia = lack of blood flow.
Reoxygenation
Reperfusion - generation of oxygen free radicals
Cell injury by Infectious organisms examples
Bacterial toxin
- Exotoxins
- Endotoxins
Hijacking of cell machinery by viral infection -> cell lysis
Collateral damage by inflammation
Cell injury by irradiation examples
Ionising
- e.g. X-rays, radioactive particles
- Generation of free radicals and direct damage to macromolecules
- different organs have different sensitivity
- v.high in bone marrow, gonads, intestines
- v.low in uterus, pancreas, adrenal
- e.g. UV-light
- can induce inflammatory response several hours after exposure
Targets of cell injury
Mitochondrial function Membrane integrity and function Protein synthesis Cytoskeleton Genetic apparatus
Mechanisms of cell injury: free radical toxicity
Highly reactive ions or molecules with single unpaired electron in outer orbital e.g. oxygen free radicals
Chain reaction with molecules in membranes to produce additional free radicals
Also damages proteins and nucleic acids - apoptosis
Detoxification by superoxide dismutase and antioxidants e.g. vitamins A, C & E
Bacterial killing by neutrophils and macrophages depends on formation of superoxide
Mechanisms of cell injury: membrane defects
Can be compromised by bacterial toxins, viral proteins, complement, cytolytic lymphocytes, and various physical and chemical agents
Increased Ca2+ in turn activates a number of enzymes, with potential deleterious cellular effects:
- ATPases (thereby hastening ATP depletion),
- phospholipases (which cause membrane damage),
- proteases (break down membrane and cytoskeletal proteins)
- endonucleases (responsible for DNA fragmentation)
Cell death
Occurs when cells are unable to achieve a new steady state following environmental insults
There are two sorts of cell death: necrosis (passive, unprogrammed) and apoptosis (active, programmed)
Necrosis
Cell death as result of lethal cell injury
Passive process
Incites an inflammatory reaction
Several distinct morphological types:
- Coagulative - most common
- Caseous - tuberculosis
- Colliquative - brain
- Gangrene - wet and dry
- Fat, fibrinoid
Coagulative necrosis
Denaturation of intracytoplasmic protein
Dead tissue becomes firm and slightly swollen
Tissue shows retention of microscopic architecture
Typical of ischaemic injury (except in brain)
Cellular proteins may leak into blood
Colliquative necrosis
Necrotic neural tissue is liable to total liquefaction and site is eventually marked by a cyst
Brain undergoes colliquative necrosis as it does not have a collagenous tissue framework.
Caseous necrosis
Characteristic of tuberculosis
Cheese like
Cellular detail destroyed in this area, which is surrounded by granulomatous inflammation.
Dead tissue lacks any structure
Gangrenous necrosis
E.g Bowel infarct- prone to develop WET gangrene
DRY gangrene - e.g Diabetes
Mechanisms of Apoptosis
(lots of info)
Apoptosis initiating factor (AIF) and cytochrome C are normally sequestered in mitochondria, but when released into the cytosol activate caspases, which are the effector molecules of apoptosis.
Two important molecules you will hear about in cancer biology are involved. P53 (the ‘guardian of the genome’) is activated by DNA damage and causes the elimination of damaged cells by apoptosis. Mutations to p53 are very common in malignant tumours, thus allowing cells to accumulate genetic abnormalities and become malignant.
Bcl-2 sequesters cytochrome C and thus inhibits apoptosis. Activating mutations leading to bcl-2 overexpression are another way that some tumours gain the ability to proliferate in an uncontrolled way.
Features of Necrosis
Multiple cells Cell size enlarged Plasma membrane disrupted Cellular contents: Enzymatic digestion; may leak out of cell Adjacent inflammation: Frequent
Cells usually Invariably pathologic (irreversible cell injury)
Features of Apoptosis
Single cell Cell size reduced Plasma membrane intact Cellular contents: Intact; may be released in apoptotic bodies Adjacent inflammation: No
Cells usually Often physiologic, means of eliminating unwanted cells
