FINAL REVIEW part 1 - Inflammation Flashcards
Ways cells adapt to stress?
1-Atrophy
2-Hypertrophy
3-Hyperplasia: more cells
4-Metaplasia: changing types (eg. mucocilliary)
5-Dysplasia: Cells are diff. sizes, nuclei diff, divide more rapidly. Prelude to cancer.
6-Anaplasia: cancer
hypoxemia vs hypoxia vs ischemia vs anemia vs anoxia
1- lack O2 in arterial blood
2- Lack O2 in tissues
3 - Restriction in blood supply to tissue
4- Decrease in total amount of Hb in blood
5- Complete deprivation of O2 in tissue
Mechanisms of cell injury (6)?
1- Depletion ATP 2- Influx Calcium 3- Mitochondrial damage and dysfunction 4- Accumulation of ROS 5- Defect in membrane permeability 6-Damage DNA/p+
Hypoxic injury steps?
decrease O2 -> decrease oxidative phosphorylation of mitochondria -> reduce ATP prod. -> Na/K pump not working properly -> increase intracellular Na -> increase attraction of H2O intracellular -> increase cellular swelling -> Ribosome on ER detach due to swelling -> impaired p+ synthesis
also: reduce ATP prod. -> anaerobic glycolysis -> increase lactic acid -> decrease pH
Also: Reduce ATP -> release of Ca2+ from ER/mitochondria stores + Ca2+ (atp dependant) pump not working -> increase intracell. Ca2+ -> Activation of Enz. -> results in: membrane damage and nuclear damage
Reactive oxygen species cause cell injury by three main reactions?
- Lipid peroxidation of membranes. Double bonds in membrane polyunsaturated lipids
- Cross-linking and other changes in proteins.
- DNA damage.
Types of necrosis?
Coagulative: cell retain barriers
Liquefactive: Full neutrophiles, result in hole in tissues, absec
Caseous: caog + liqu necrosis, cheese like. In tuberculosis
Gangrene: Ischemic necrosis followed by bacterial attack
Apoptosis characteristics?
1-requires active RNA/p+ synthesis
2-Cell quickly replaced
3-No inflammation
Necrosis characteristics?
- Cell and organelles swell
- Membrane blebs
last longer than apoptosis - Followed by inflammation
Apoptosis execution in two pathways?
1- Intrinsic - mitochondria: Lack growth factors/DNA damage/misfolded proteins -> Bcl-2 family sensors activation -> activation of effectors Bax and Bak -> These dimerize and create passage in mitochondria which allows for leakage of cytochrome C + cofactors -> Initiator caspases -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis
2- Extrinsic - 2.1Death receptors: Fas ligand (for Fas) ->Activation of death molecules on cell surface (mainly part of Tumor Necrosis Factor receptor family with a death domain inside the cell) Fas with a death domain -> Fas trimerize -> Creating the FADD (Fas Activating Death Domain) with 3 death domain inside the membrane -> Activation of caspase cascade -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis
2.2: TNF binds to TNF receptor 1 (TNFRI) -> Creating the TRADD -> FADD -> Activation of caspase cascade -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis
Acute inflam. steps?
1- Recognition of microbe, necrotic cells and foreign substances
2-Vascular changes: INcreased blood flow due to vasodilatation + increase vascular permeability
3-Leukocyte Recruitment :
4- Leukocyte Activation
Transudate vs exsudate
Almost no p+, few blood cells
high p+, and lots blood cells
- Leukocytes recruitment steps?
- Margination and rolling: Margination = when WBC accumulate near periphery of vessels. Weak/transient interaction between leuko. and endothelial cells = mediated by SELECTINS (found on both). Expressed on endothelial by stimulation of histamine and thrombin
- 2 Adhesion: Binding of INTEGRINS (on both WBC and endo. cells) causes firm adhesion
- 3 Transmigration: Neutro. go between cells, then secrete COLLAGENASES to breakdown the basement membrane.
- 4 Chemotaxis: Leuko. follow gradient of [].
Phagocytosis stages
- Recognition and attachment: TLR, Fc portion of IgG
- Engulfment: Membrane zip up around microbe. This becomes a phagosome inside the cytosol. Lysosome (with ROS and Enz.) fuse to the phagosome, becoming a phagolysosome
- Killing and Digestion
Two major sources of inflammatory mediators?
1- Cell derived: Either preformed stocked in granules and secreted or de novo produced
2-Plasma p+-derived: Major source is the liver (Complement, Kinins, clotting system)
Activation of complement system (3 pathways)?
- Classical : 2IgG activating C1
- Alternative: ON its own
- Lectin:
