lecture 1 Flashcards
where are the cell bodies of the pre-ganglion located
in the brain stem
where are the cells bodies of the post-ganglionic fibres located
embedded in walls of bronchi and bronchioles
What happens when posganglionic cholinergic fibres are stimulated
- Bronchial SM contraction
- mediated by M3 muscarinic ACH receptors on airway smooth muscles
- increased muscous production is mediated by M3 muscarinin ACh receptors on goblet cells
What happens when post ganglionic noncholinergic fibres are stimulates
- bronchial smooth muscle relaxation
- mediated by nitric oxide and
- Vasoactive intestinal peptide
is there inervations to bronchiole smooth muscle
- parasympathetic inervation
- no sympathetic inervation to bronchial smooth muscle
- but post-ganglionic fibres supply submucosal glands and smooth muscle of arterioles
- indirectly mediated
Parasympathetic division the airway sm
- inervates bronchioles smooth muscles and submocosal glands
Stimulation causes:
- bronchiole SM contraction
- inreaces mucous secretion
- both medaited by M3 muscarinic ACh receptors
Sympathetic supply to to bronchioles
- no innervation of broncial sm but muscosal glands and arerial sm
Stimuation causes:
- Bronchioles sm relaxation via B2-adrenoceptors on airway smooth muscles by adrenaline
- decreased muscous secretion via B2 adrenoceptors on goblet cells
- Increaes mucocillary clearance via B2 adrenoceptors on epithelial cells
- vascular sm contraction - a1 adrenoceptors on sm
What is the mechanism of bronchiole smooth muscle contraction
G/q11 pathway
- binding of acytyl choline onto M3 Ach receptors
- this G-protien coupled receptor activates the enzyme phospholipase C
- which converts PIP2 into IP3
- IP3 diffuses into cytoplasm and binds to IP3 receptor (ca+ channel) in sarcoplasmic reticulum of smooth muscle cells
- this allowx entry of Ca+ ions into the cytoplasm
- increased intracellualr calcium = contraction
What is the 2nd mechanism of this
- voltage gated calcium channels - open due to depolarisation
- calcium entres cytoplasm down its electrochemical gradient
- induces Ca+ channel to open in the sarcoplasmic memrbane
- increased calcium = contraction
What is the initiation of contraction by Ca2+ in smooth muscles
- increased intracellular calcium levels
- 4 ions of calium bind to calamodulin (regulatory protien) to form Ca2+-calamodulin complex
- binds to myosin light chain kinase
- activated causes phosphorylation of inactive myosin cross bridge
- phosphorylated form binds to actin
- permits interactions between myosin and actin in muscle cells
- contraction
How does relaxation of airway smooth muscle occur
- Dephosphorylation of myosin light chain
- By myosin phosphatase - carries out dephosphorylation
- Relaxation requires return of Ca2+ to basal levels
What is the mechanism for smooth muscle relaxation
Gs pathway
- B2-adrenoceptor binds adrenaline
- stimulations leads to Gs protien
- Gs activate the enzyme Adenlylate cyclase which converts ATP to cyclic AMP
- CAMP activates protien kinase A which has 2 Funtions:
- Inhibits myosin light chain kinase from by phosphorylating it- opposes contraction
- phosphrylates and stimulates myosin phosphatase allows dephosphorylation of MLCK - speeds up relaxation
What is the result of provocation tests on normal people , mild asthmatics and severe asthmatics
Mild asthmatic
- Hypersensitive - concentration of bronchoconstrictor to produce a fall in FEV1 is less than in normal indiviudal
- Hyper-reactive - Greater fall in FEV1 compared to normal
Sever Asthmatic : relationship is shifted even more to the left
What is the immediate and delayed phase of asthma
Type 1 hypersensitivity reaction
- early phase bronchospasm
- acute inflamation
Type 2 hypersensitivity reaction
- Late phase bronchospasm
- chronic inflammation
What is the difference between atopic and non-atopic asthma
Non-atopic
- TH1
- IgG
Atopoc
- TH2
- IgE
What is the Induction phase in development of atopic asthma
- Allergen is presented by dentritic cells to CD4+ T cells
- which matures into TH2 cell and TH1
- but both are incompatible with each other supresses each other
- TH2 forms physical contact with plasma cells and also releases IL-4 to stimulate plasma cells
- plasma cells synthesise IgE antibodies
What is the Effector phase in the development of atopic asthma
- IgE binds to eosinophils and Mast cells
- TH2 release
- IL-5 - activates eosinophils
- IL-4 - activation and differentiation into plasma cells
- IL-4 + IL-13- activates Mast cells in airway tissue
What happens when a mast cell is activates
- Allergen binds to IgE recepto
- Stimulates:
- Calcium entry into mast cells
- Release of calcium from intracellular sotre evoking:
- release of secretory granules containing histamine
- LTC4 and LTD4 - sm contraction
- release of other inflammatory mediators that cause attaction on inflammatory cells into that areea
Key events
