L3- Cell injury Flashcards Preview

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Flashcards in L3- Cell injury Deck (19):
1

Increased cellular activity

Hyperplasia
Hypertrophy

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Decreased cellular activity

Atrophy

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Change in cell morphology

Metaplasia
reversible replacement of one differentiated cell type with another differentiated cell type.

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Aetiology of cell injury

Oxygen availability
Physical trauma
Chemical agents
Infectious organisms
Irradiation

Others:
-Immunological
-Lack of essential nutrients/vitamin
-Genetic disorders
-Ageing

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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

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Cell injury by Infectious organisms examples

Bacterial toxin
-Exotoxins
-Endotoxins

Hijacking of cell machinery by viral infection -> cell lysis

Collateral damage by inflammation

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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

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Targets of cell injury

Mitochondrial function
Membrane integrity and function
Protein synthesis
Cytoskeleton
Genetic apparatus

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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

10

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)

11

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)

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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

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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

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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.

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Caseous necrosis

Characteristic of tuberculosis
Cheese like

Cellular detail destroyed in this area, which is surrounded by granulomatous inflammation.

Dead tissue lacks any structure

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Gangrenous necrosis

E.g Bowel infarct- prone to develop WET gangrene

DRY gangrene - e.g Diabetes

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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.

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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)

19

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