ILA Flashcards
Structure of an atherosclerotic plaque
Lipid, Necrotic core, Connective tissue, Fibrous “cap”
Stimulus for an atherosclerotic plaque
Adhesion- Chemoattractants released from leukocytes
Examples of non-modifiable risk factors for atherosclerosis
Age, gender, race, family history, Type 1 diabetes
Examples of modifiable risk factors for atherosclerosis
smoker, lack of exercise, weight, (borderline) type 2 diabetes, hypertension, high cholesterol
Risk factor for atherosclerosis- smoking
Releases free radicals, nicotine + CO into the body/blood
-These damage endothelial cells
Risk factor for atherosclerosis- hypertension
Increased pressure 🡪 increased damage of the wall
Risk factor for atherosclerosis- diabetes
-High glucose levels in the blood
-Increased Free radicals
-Increased oxidation of LDLs 🡪 means they get stuck
-Loss of nitric oxide (NO)
-Which normally allows relaxation of vessel + increased flow
-Promotes platelet aggregation
Risk factor for atherosclerosis- cholesterol
High LDLs
-Can pass in and out of the arterial wall in excess, accumulates in arterial wall, undergoes oxidation and glycation
Risk factor for atherosclerosis- Obesity
Increases proinflmmatory cytokines
Risk factor for atherosclerosis- Exercise
-Helps rebalance of low- and high-density lipoproteins
-Reduces blood pressure
Pathophysiology of atherosclerosis
- Endothelial cell dysfunction
- High levels of LDL in the blood
- Inflame (activate) endothelial cells (leukocytes)
- Macrophages take up lipid to form foam cells
- Foam cells
- Formation of a fatty streak in intimal layer
- The activated macrophages (release products - cytokines and growth factors)
- Smooth muscle proliferation (to intima) around the lipid core 🡪 formation of a fibrous cap (collagen)
- Plaque either: -Occludes lumen 🡪 angina
-Ruptures
-Result of inflammatory conditions
-When the plaque ruptures
-Platelets adhere and clotting process begins
Role of macrophages in atherosclerosis
take up lipid (oxidised LDLs) to form foam cells (inflammatory response)
Main 3 coronary arteries to be occluded
-LAD (left anterior descending)
-Right coronary A
-Left circumflex
Role of foam cell in atherosclerosis
-Promote migration of SMCs from tunica media 🡪 tunica intima
-When foam cells die 🡪 Lipid content released 🡪 plaque growth
Secondary preventative measures- atherosclerosis
Statin, antihypertensive, diabetes control (meds, carbs intake), social prescribing
Primary preventative measures-atherosclerosis
Exercise more, eat more healthily, stop smoking
Define anaphylaxis
Anaphylaxis a severe, life-threatening, generalised or systemic hypersensitivity reaction which is likely when both of the following criteria are met:
-Sudden onset and rapid progression of symptoms.
-Life-threatening airway and/or breathing and/or circulation problems usually associated with skin and mucosal changes
Symptoms of anaphylaxis
Occurs within minutes and lasts 1-2 hours
Vasodilation
Increased vascular permeability
Bronchoconstriction
Urticaria (hives)
Angio-oedema (rapid, oedema, or swelling, of the area beneath the skin or mucosa)
Common triggers of anaphylaxis
Foods, venom (bee/wasp stings), drugs, contast agents
Common triggers of anaphylaxis- Foods
peanuts, pulses, tree nuts (brazil nuts, almond, hazlenuts), fish and shellfish, eggs, milk, sesame
Common triggers of anaphylaxis- Drugs
antibiotics, opoids, NSAIDs, muscle relaxants (Baclofen, Diazepam), contrast agents (used in x-rays)
Pathophysiology of anaphylaxis- Sensitization phase
- Exposure to allergen results in IgE for the allergen binding to mast cells and basophils, they are primed to react for the next time the cells come into close proximity with the allergen
Ig that mediates type 1 hypersensitivity reactions
IgE mediated
IgE antibodies
formed to an antigen (or allergen), with an individual’s tendency towards making IgE being determined by factors including: genetics, T cell responsiveness and antigenic burden
Pathophysiology of anaphylaxis- re-exposure phase phase
-Re-exposure to allergen causes cross-linking of IgE on the cell surfaces causes rapid (mast cell) cellular degranulation and liberation of a number of chemical mediators (most importantly histamine)
- Reaction of antigen with IgE on mast cells also stimulates synthesis and release of platelet activating factor (PAF), leukotrienes and prostaglandins
Mediators released from mast cell degranulation
preformed molecules histamine, protease enzymes, proteoglycans and chemotactic factors
Physiologic responses to the release of anaphylaxis mediators
Smooth muscle spasm in the respiratory and GI tracts
Vasodilation- makes you feel hot and itchy
Increased vascular permeability
Stimulation of sensory nerve endings
Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway oedema
Cardiovascular effects result from decreased vascular tone and capillary leakage
Physiologic responses to the release of anaphylaxis mediators- CV effects
Cardiovascular effects result from decreased vascular tone and capillary leakage. Hypotension, cardiac arrhythmias, syncope and shock can result from intravascular volume loss, vasodilation and myocardial dysfunction, increased vascular permeability can produce a shift of 35% of vascular volume to the extravascular space within 10 minutes
H1 receptors action
-Vasodilation, hypotension, and flushing are mediated by H1 receptors
-H1 receptors alone mediate coronary artery vasoconstriction, tachycardia, vascular permeability, pruritus (itchy skin), bronchospasm, and rhinorrhoea (runny nose)
H2 receptors action
H2 receptors increase atrial and ventricular contractility, atrial chronotrophy, and coronary artery vasodilation
Rapid assessment for anaphylaxis- ABCDE
Airway: look for and relieve airway obstruction. Remove any traces of allergen
Breathing: look for a treat bronchospasm and signs of respiratory distress
Circulation: colour, pulse, BP
Disability: assess whether responding or unconscious (AVPU)
Exposure: assess skin with adequate exposure, but avoid excess heat loss
When to consider anaphylaxis
when there is compatible history of raid-onset severe allergic-type reaction with respiratory difficulty and/or hypotension, especially if there are skin changes present
1st line treatment for anaphylaxis
IM Adrenaline (epinephrine)
Adrenaline (epinephrine) action for treatment of anaphylaxis
Stimulation of beta1-adrenoceptors: positive ionotropic (force of heart contraction) and chronotropic (heart rate) effects on the heart
Stimulation of beta2-adrenoceptors: reduces oedema and brocnhodilates
Attenuates further release of mediators from mast cells and basophils by increasing c-AMP(cellular signal induction) and so reducing the release of inflammatory mediators
Why give IV fluids after an anaphylactic shock
To help restore the circulating volume and therefore the stroke volume thus increasing the cardiac output
Action of Chlorphenamine after initial resus for anaphylaxis
Chlorphenamine is an antihistamine which blocks the Histamine 1 receptor thus blocking the action of the histamine released during anaphylaxis
Action of Hydrocortisone after initial resus for anaphylaxis
Suppresses prostaglandin and leukotriene mediators, inflammatory cell recruitment and migration are inhibited and vasoconstriction reduces leakage from the blood vessels
Explain why a second dose of adrenaline might be required for treatment of anaphylaxis
Adrenaline has a short half life therefore a second dose may be required if the symptoms of not initially respond or get worse
What blood test will you need to take to confirm an anaphylactic shock
Serum mast-cell tryptase can be measured in cases of anaphylaxis. Tryptase is the preferred marker for demonstrating mast-cell degranulation
Risk factors for anaphylaxis
Middle to older age
Previous anaphylaxis.
Allergies or asthma.
Certain other conditions- These include CVD and an irregular accumulation of a certain type of white blood cell (mastocytosis)
