4.8 - Anaphylaxis

Question 1

What is anaphylaxis?

Answer 1

• acute (immediate) type I hypersensitivity reaction that can be systemic, and is sometimes so overwhelming it is life-threatening
• results from a response to an allergen that is present throughout the body
• substances which cause anaphylaxis in susceptible patients are those which can pass freely around the body e.g:
• penicillin - especially if given intravenously
• certain other drugs e.g. oral anaesthetics, X-ray contrast agents
• venom in bee/wasp stings
• peanuts - the allergen can be absorbed fast enough to cause systemic effects

Question 2

What type of cell causes these symptoms?

Answer 2

• mast cells
• released as a progenitor from bone marrow
• home to connective and mucosal tissues where it matures
• noted for its many granules

Question 3

What is the signalling molecule involved?

Answer 3

• histamine
• mast cells are widely distributed throughout the body in both connective tissue (e.g. under skin) and in association with epithelial mucosae (e.g. the respiratory and intestinal epithelia)
• mast cell granules contain several inflammatory mediators, notably histamine and leukotrienes
• inflammatory mediators act principally on blood vessels and smooth muscle which express specific histamine receptors (GPCRs)
• in connective tissue, histamine causes dilatation of vessels with increased blood flow to the surface and increased movement of fluid out of the bloodstream (oedema)
• around mucosae, the opposite occurs, causing constriction of airways and contraction of smooth muscles in the walls of the intestine
• net effect depends on whether the stimulation is local or systemic

Question 4

What immunoglobulin class is likely to be involved?

Answer 4

• IgE binds with high affinity to Fc receptors of mast cells
• present at extremely low levels in the blood
• produced in response to parasitic infections and in allergic diseases
• cross-linking by antigen to IgE triggers mast cell activation and histamine release

Question 5

What causes the rashes and puffy skin?

Answer 5

• in connective tissue, histamine causes dilatation of vessels with increased blood flow to the surface and increased movement of fluid out of the bloodstream (oedema)
• rash (urticaria) is an acute response to allergen raised lump or wheal
• caused by animal hair, proteins in natural latex, certain chemicals, substances in insect and plant stings

Question 6

How does hay fever and asthma work?

Answer 6

• if allergen inhaled, principal site of action will be mucosal mast cells of the respiratory system
• if this is principally in the nasal passages, the effect will be oedema in the epithelia lining the nose and a consequent general irritation inluding stimulus of mucus secretion
• it is the allergic reaction which causes hay fever (rhinitis)
• if allergen reaches bronchioles, there will be contraction of smooth muscles = reduced diameter of airways, inflammation and increased mucus production –> asthma
• substances known to be capable of causing hay fever and asthma include pollens, faeces of dust mites, and proteins from animal hairs

Question 7

How do food allergies work?

Answer 7

• if allergen is ingested, then it will act at mucosal mast cells in the intestinal tract
• stimulation of associated smooth muscle leads to the vomiting and diarrhoea typical of a food allergy
• if allergen can be absorbed and passed into bloodstream, it may also cause skin symptoms (rashes / itching)
• substances known to be capable of causing food allergies include peanuts and other nuts and legumes (e.g. soya), shellfish, milk, eggs and wheat

Question 8

Why should adrenaline have been given?

Answer 8

• anaphylaxis results from a systemic response to the allergen
• dilatation of peripheral blood vessels results in a dramatic drop in blood pressure (hypotension) which can affect organ function due to reduced blood flow - known as shock
• constriction of bronchi = difficulty breathing
• patient responds with increase in respiratory and heart rates; there may also be symptoms of nausea, abdominal cramps or diarrhoea (from effects on intestines)
• an injection of adrenaline will act to constrict peripheral blood vessels and redirect blood to organs
• patient lain down with feet raised in order to improve blood supply to head and trunk

Question 9

What sorts of drugs might have been in the subsequent injections?

Answer 9

• in mucosal tissues of the lung, histamine release causes constriction of bronchi –> breathing difficulties = patient responds with increase in respiratory and heart rates etc
• anti-histamines e.g. diphenydramine
• corticosteroids e.g. hydrocortisone
• if breathing problems persist, oxygen may be necessary and bronchodilators may be given via an inhaler e.g. salbutamol
• long term treatment - avoiding allergens, adrenaline in a self-injection pen e.g. EpiPen

Question 10

Why did the patient feel faint?

Answer 10

• due to dramatic drop in blood pressure (hypotension)
• syncope (fainting) is a temporary loss of consciousness usually related to insufficient blood flow to the brain
• legs raised counteracts this

Question 11

Why was blood pressure monitored in hospital?

Answer 11

• monitoring of BP provides a reliable indication of recovery
• occasionally the symptoms return (usually within hours of initial reaction) - known as biphasic anaphylaxis
• patients with moderate respiratory / cardiovascular compromise should be observed for 8-10 hours before discharge