Asthma Flashcards
Characteristics of asthma (5)
Inflammatory response: eosinophils, mast cells and neutrophils
Hyperresponsiveness of smooth muscle to substances that cause contraction of the smooth muscle, such as acetylcholine, histamine and PAF.
Hyporesponsiveness of the smooth muscle to substances that relax smooth muscle, such as adrenaline.
Neuronal imbalance
(smooth muscle) Hyperplasia and hypertrophy
Describe alterations to smooth muscle
(i) abnormalities in conduction properties;
(ii) alteration in calcium control and contraction/ relaxation
(iii) proliferative response increases
Describe structural changes
Includes: variety of gross morphological changes e.g. epithelial damage, mucosal oedema, increased intraluminal secretions, basement membrane thickening, smooth muscle hypertrophy and hyperplasia and inflammation
morphology of bronchial asthma
what happens to the gap junctions in asthma
Lungs are over-distended due to over-inflation
Small areas of atelectasis can be seen
Occlusion of bronchi and bronchioles by thick tenacious mucous plug:- most striking finding.
Cells become single unit in nature and there is an increased occurrence of gap
junctions
How does calcium enter cells?
Name an endogenous bronchoconstrictors
Explain progress of contraction
- via voltage- and receptor-operated calcium channels
- from sarcoplasmic reticulum stores.
Acetylcholine: activation Gq –> PLC activates PKC –> cytoplasm. In SR combines with calmodulin & activates myosin light kinase through P = contraction
Describe proliferative response in asthmatics
- what can activate this pathway?
Growth factors elicit mitogenesis and cell proliferation.
Bronchoconstrictors can activate this pathway at several points including raf-1 kinase and MAP kinase.
Describe cholinergic innervation via release of Ach
Name an inflammatory mediator which can modulate adrenergic control
Defects in cholinergic innervation:
(a) increased vagal tone.
(b) reflex bronchoconstriction.
(c) increased acetylcholine release: increased neurotransmission that is facilitated by tachykinins, thromboxanes and serotonin. Adrenergic nerves inhibit acetylcholine release, suggesting defects in b- or a2 receptor function.
(d) increased post-synaptic muscarinic receptor function.
- e.g histamine
Inflammatory response
Name early phase
Inflammatory cells are
recruited to pulmonary arteries & enter into
the interstitial fluid & smooth muscle by squeezing
through the endothelium = diapedesis.
Inflammatory response
Name late phase
Inflammatory cells attach to
epithelium & squeeze through lining into
airway tubule. The release of substances such as O2,
major basic protein and PAF have a potent killing effect
upon the epithelial cells and extensive damage to the
epithelial lining is achieved.
Cells involved in asthma
Mast cells: respond to allergen & IgE via histamine release, TNFa, LTD4, & interleukins
such as IL1.
Neutrophils and basophils
Macrophage: these cells release prostanoids, cytokines
and leukotrienes.
Eosinophils: release PAF, TNFa, O2., CSF
(which causes haematopoetic stem cells to differentiate
into progenitor cells), GMSCF (which causes progenitor
cell to differentiate into eosinophils) and MBP.
Name asthma Adhesion molecules
(i) Integrins composed of a & B sub-units, CD11/CD18 complex expressed upon leukocytes.
(ii) immunoglobulin family: i.e ICAM-1 and ICAM-2 expressed on endothelial cells.
(iii) Selectins (can bind siayl lewis X oligosaccaride/lacto-N-fucopentose III (CD15) moities on leukocytes):
ELAM/E-selectin
GMP-140/P-selectin
Mel-14/L-selectin (lymphocytes)
Name some treatments in asthma
PA2 inhibitor, GC
Indonethacin inhibits: Prostanoid production from arachidonic acid
Thromboxane antagonists- reverse antigen induced asthma.
Leukotriene antagonists
Histamine antagonists
PAF antagonists
