MISC Flashcards
Describe the fever response
(1) Pyrogens can be either endogenous e.g. IL-1 or IL-6 or exogenous i.e. endo or exotoxins from bacteria
(2) Pyrogens travel to pre-optic hypothalamus and increase activity of phospholipase A2 which releases arachidonic acid from phospholipid bilayer.
(3) AA is then converted to prostanoids via cyclo-oxygenase
(4) PGE2 increases the temperature set point of the hypothalamus resulting in the following physiological responses:
(i) Increased metabolism
(ii) Increase thermogenesis
(iii) Increased rigors
(iv) Peripheral vasoconstriction
Describe the process of phagocytosis
Recongition + Attachment
Engulf
degrade
1.Pathogen is recognised via C3b opsonin/ Fc portion of IgG and phagocyte can attach with corresponding receptors.
2.Phagocyte engulfs the pathogen containing it in a phagosome.
3.A phagolysosome is formed by fusing of phagosome with lysosome.
4.Reactive oxygen species are produced: O2 –> superoxide –> hydrogen peroxide –> hypochorous acid by NADPH oxidase, superoxide dismutase and myeloperoxidase respectively.
a.Other option is lysosome enzymes can puncture holes in membrane.
5.Catalase breaks hydrogen peroxide down to water and oxygen.
6.Dead microorganisms can be degraded by acid hydrolases.
Describe the cellular events of leukocyte migration
Margination and rolling
- Vasodilation and increased vascular permeability contribute to loss of plasma contents across the endothelium causing an increased viscosity of the blood.
- The slower rate of blood flow allows for the margination of nearby leukocytes toward the endothelial lining.
- P + E selectin expression on vascular endothelium is increased in response to mediators such as histamine and TNF-a.
- Sialyl-lewis X binds to the selectins and the leukocyte rolls along towards its point of entry.
Adhesion
- Adhesion molecules stops rolling and anchors the leukocyte before it can transmigrate.
b. LFA-1 -> ICAM-1 Integrins
c. VLA-4 -> VCAM-1 Integrins - Conformational change in these adhesion molecules in response to chemokines allows for firm adhesion.
Transmigration and diapedesis
- At the post-capillary venules, transmigration of the leukocytes across the vessels is mediated by PECAM-1
Chemotaxis
-The leukocytes are directed towards the site of infection by various mediators e.g. IL-8, bacterial endotoxins, complements.
What is meant by “steady state”
Steady state occurs when the rate of drug absorption is equal to the rate of drug elimination when given at continuous or repeated dose. This means that levels of the drug in the blood remain stable.
Describe the 4 ways by which bacteria can gain resistance to antibiotics
- Vertical Evolution: The process by which antibiotic resistance arises through mutations in the bacterial DNA during replication. These mutations are passed on to offspring during cell division, leading to the inheritance of resistance traits.
- Horizontal Evolution: The transfer of antibiotic resistance between bacteria, not through offspring, but by direct exchange of genetic material. This can occur through three mechanisms:
(i) Conjugation: Transfer of plasmids (which may carry antibiotic resistance genes) from one bacterium to another through direct cell-to-cell contact.
(ii) Transduction: Transfer of bacterial DNA, including antibiotic resistance genes, via bacteriophages (viruses that infect bacteria).
(iii) Transformation: Uptake of free DNA, including resistance genes, from the surrounding environment by a bacterium, usually from dead or lysed bacteria.
name 5 mechanisms by which resistance manifests
(i) Overproduction of the target
(ii) Change the structure of the target
(iii) produce enzymes that inhibit the antibiotic
(iv) Efflux pumps
(v) Bypass the step that is inhibited
Define necrosis and Differentiate between coagulative and liquefactive necrosis
Necrosis is the forced, disorderly cell death within living tissue.
Coagulative necrosis is the main type that occurs after prolonger ischemia. Tissue maintains its basic architecture initially with eosinophilic cells visible for days to weeks. Denaturation of structural proteins and enzymes means that proteolysis of the death cell does not occur. Inflammatory cells release lysosomal enzymes and phagocytes then clear the cellular debris.
Liquefactive necrosis is necrosis commonly associated with infection and inflammation. It is associated with ischemia within the CNS. Presence of digestive enzymes give the area a liquid appearance. There is loss of normal architecture and structure with abundant cellular debris. The debris is eventually phagocytosed.
Necrosis is generally associated with exposure of cellular contents to the extracellular environment due to loss of plasma membrane integrity. This is in contrast to apoptosis which is planned, ordered and causes chromatin condensation, cellular fragmentation forming apoptotic bodies and phagocytosis by macrophaeges.
Describe phase I metabolism
Phase I metabolism involves an oxidation reactions carried out by CY450 enzymes to make a drug more water soluble.
2 electrons from NADPH are used.
1 oxygen molecule attached to drug, while another is reduced to water
Describe phase II metabolism
Drug or its phase I metabolite are conjugated to endogenous substrates via covalently bonds to make them more water soluble
(1) Glucoronidation
Drug/metabolite with UDP glucoronic acid by UDP-glucoronyl-transferase
(2) Sulphation
Drug/metabolite with PAP’s by sulfotransferase
(3) Glutathione conjugation
Drug/metabolite to glutathione by glutathione-s-transferase
