PCC2 Special Senses - The Ear

Vestibular system Includes the parts of the inner ear and brain that process the sensory information involved with controlling balance and eye movements. Motion sickness - Most commonly diagnosed vestibular disorder - Can affect any individual and involve any form of movement, from moving vehicles to fairground rides - Exact prevalence is unknown - Children between 2-12yrs are mostly affected Epidemiology - Motion sickness - Women are affected more than men - Certain sectors of the population show higher prevalence rates e.g., naval crew and pilots Pathophysiology - Motion sickness Results from the inability of the brain to process conflicting information received from sensory nerve terminals concerning movement and position - the sensory conflict hypothesis. It is a symptom complex characterised by: - Nausea - Pallor Signs and symptoms of Motion sickness - Vague abdominal discomfort - Occasionally vomiting - Fatigue, weakness and an inability to concentrate can also be experienced - First generation antihistamines = e.g., cyclizine, cinnarizine and promethazine Motion sickness - Treatment - Anticholinergics = e.g., hyoscine and scopolamine 1/7 Side effects of Antihistamines & Hyoscine ? - Dry mouth - Sedation Hyoscine hydrobromide - Anticholinergic agent - Prophylactic drug of choice for motion sickness - Similar in structure to atropine - Both hyoscine and acetylcholine possess a basic nitrogen and an ester (COOC) group Why is hyoscine able to bind to the cholinergic receptor when its structure is - The distance between the 2 groups is unrelated to acetylcholine ? also the same (approximately 5.3Å) - Hyoscine is a larger molecule than acetylcholine = can bind with other regions within the cholinergic receptor binding site that do not interact with acetylcholine itself Why does hyoscine not act as an agonist - Differing interaction with the receplike acetylcholine ? tor = leads to different conformational changes taking place - This leads to binding with no subsequent activity = a switch from agonist to antagonist Hypersensitivity reaction Unwanted immune responses Immediate or Anaphylactic hypersensitivity: - Individuals will show an allergic response to allergens - T-helpers will convert into Th2 cells = results in stimulation of B cells that will begin to produce IgE antibodies 2/7 - IgE antibodies are associated with allergy and these individuals will express more IgE antibodies compared to someone without allergies Hypersensitivity reaction - Type 1 - Localised type 1 responses result in problems e.g., hay fever, urticaria, triggering asthma attacks - More generalised responses can cause anaphylactic shock Antibody-dependent cytotoxic hypersensitivity: - Immune reactions are directed against an individual's cells that have the appearance of being non-self. Hypersensitivity reaction - Type 2 - The resulting antigen-antibody reactions cause these cells to come under attack E.g.,: - Neutrophils being attacked to cause agranulocytosis - Platelets attack causing thrombocytopenic purpura and possibly autoimmune thyroiditis (Hashimoto's disease) Complex-mediated hypersensitivity: - antibodies and soluble antigens react and form complexes Hypersensitivity reaction - Type 3 - complexes can then activate complement or attach to special cells, mast cells, to cause inflammatory mediators to be released. 3/7 Examples - some types of autoimmune arterial and renal diseases and Farmer's lung (exposure to hay mould) Cell-mediated hypersensitivity: - Involves the activation, proliferation and mobilisation of antigen-specific T cells - Reaction takes time to occur = delayed-type hypersensitivity Hypersensitivity reaction - Type 4 - Large amounts of cytokines are released from activated T-cells = recruit large numbers of leukocytes that can go on to cause damage E.g., Rheumatoid arthritis, multiple sclerosis and type 1 diabetes. A - anaphylaxis C - cytotoxic I - immune complex D - delayed type What acronym can be used to remember the 4 classes of hypersensitivity reaction ? Mast cells - A specialist cell involved with the release of inflammatory mediators - Can be stimulated when they come into contact with allergens - Main mediator released = Histamine 4/7 - On first exposure to an allergen = body will synthesise IgE antibodies - IgE antibodies will attach themselves to mast cell Fc receptors - In re-exposure to the same allergen, cross-links will form between the IgE anDescribe what happens when a mast cell tibodies triggering an influx of Ca2+ ions undergoes stimulation ? - This then enables histamine to be released (can be seen as a process of degranulation) Formed from the essential amino acid histidine by histidine decarboxylase. How is Histamine formed ? Found mostly in body tissues - stored as granules in mast cells and basophils. Where can Histamine be found in the body ? H1 - Smooth muscle and inflammatory effects What four main receptors are involved in H2 - Mostly gastric acid production mediating the actions of Histamine ? H3 - CNS actions H4 - Immune response regulation Histamine actions mediated by the H1 receptor ? Smooth muscle and inflammatory effects 5/7 Histamine actions mediated by the H2 receptor ? Mostly gastric acid production Histamine actions mediated by the H3 receptor ? CNS actions Histamine actions mediated by the H4 receptor ? Immune response regulation When can the triple response be deter- Following an intradermal injection of hismined ? tamine Flush - within 10 seconds reddening occurs at the site, resulting from small arteriolar vasodilation Wheal - local oedema then occurs, due to increased postcapillary venule permeability Triple Response of Lewis Flare - a diffuse mottled reddening develops around the area, due to arteriolar dilatation caused by a sensory nerve reflex What receptor does histamine act on to cause the inflammatory effects included in the Triple response (flush, wheal and flare) ? H1-receptors - Vasodilatation increases blood flow = increases the delivery of leukocytes to an area, helping fight an infection. Under normal circumstances, how does histamine acting on H1-receptors aid - The increased venule permeability fighting infections ? means it is easier for leukocytes to leave the blood, migrate into tissues and hunt for invading substances. How are hypersensitivity reactions treat- Using H1-receptor antagonists = antihised ? tamines - They do not stop histamine from being released, instead they block these receptors 6/7 - Histamine is not unable to stimulate tissue as much = therefore reduces it symptoms MOA of Antihistamines 7/7