Week 11 Flashcards
Asthma: definition?
Severe attacks can cause…
3 essential features
Defined as: recurrent, reversible airway obstruction
Attacks of wheezing, shortness of breath
Often nocturnal dry cough
Severe attacks can cause hypoxaemia
3 features:
- Airway inflammation
- Bronchial hyper-responsiveness
- Recurrent, reversible airway obstruction
Pathogenesis of asthma?
3 important mediators
Activation of the Th2 profile of cytokine production in genetically susceptible people
– Attracts inflammatory granulocytes (eosinophils) to mucosal surface
– IL-5 and GMCSF cause eosinophils to produce cysteinyl leukotrienes
and release granule proteins
– IgE synthesis is promoted, as is expression of IgE receptors on mast
cells and eosinophils
Important mediations:
– leukotriene B4 and cysteinyl-leukotrienes (C4 and D4)
– interleukins IL-4, IL-5, IL-13
– tissue damaging eosinophil proteins
What is the part played by t-lymphocytes in allergic asthma?
- The allergen activates CD4 t cells
- This then forms a Th2 helper cell
- These produce plasma cells which produce IgE antibodies
- IgE antibodies stimulate expression of IgE receptor on mast cells and eosinophils
Describe the immediate phase of asthma?
Inhibited by?
- Eliciting agent (allergen/ non-specific stimulus)
- Activates mast cells
- Produces chemotaxins/chemo kines and Spasmogens/cysLTs/H1PGD2
- Spasmogens /cysLTs/H1PGD2
- BRONCHOSPASM
Inhibited by: B2-adrenoceptor agonist, CysLT-receptor antagonist and theophylline
Describe the late phase of asthma?
Inhibited by?
- Infiltration of cytokine-releasing Th2 cells, and monocytes, and activation of inflammatory cells, particularly eosinophils
- Produces mediators (e.g. cysLTs) and EMBP/ECP
- Airway inflammation, airway hypersensitivity
- BRONCHOSPASM, WHEEZING, COUGHING
Inhibited by: Glucocorticoids
What is consequence of eosinophils infiltration in to airways in asthma?
Thickened BM
Oedema
Mucus plug formation with sequamated epithelial cells
Treatment and management of asthma
Anti-asthmatic drugs include bronchodilator and anti-inflammatory agents
Treatment is monitored by measuring peak expiratory flow rate
Name 5 main groups of drugs used to treat asthma? Examples
- B2-adrenoceptor agonists
– short-acting (SABA), e.g. salbutamol
– long-acting (LABA), e.g. salmeterol - Anti-inflammatory agents
– Glucocorticoids, e.g. beclometasone, budesonide - Cysteinyl leukotriene antagonists (LTRA)
– Montelukast - Methylxanthines
– theophylline and derivatives - Anti-IgE treatment
– Omalizumab
B-adrenoreceptors agonists
Mechanism?
SABA vs LABA?
Mechanism:
- Dilate bronchi via smooth muscle b2 receptors
- Physiological antagonists of the airway spasmogenic mediators
- Have little effect on bronchial hyper-reactivity
Short acting (SABA) e.g. Salbutamol
– given by inhalation
– effects start immediately and last 3-5 hours
– “ Rescue remedy”: treats wheeze in patients
Long acting (LABA) e.g. Salmeterol
– lasts longer (8-12 hours)
– given to prevent bronchospasm (at night or during exercise) in patients
requiring long-term therapy
Glucocorticoids (ICS) Action? Decrease... Given by \_\_\_\_ e.g. In deterioration asthma, use? Administration?
Main drugs used for anti-inflammatory action in asthma
– not bronchodilators but prevent the progression of chronic asthma
– don’t prevent the immediate response to allergen or other challenges
They decrease:
– formation of cytokines (particularly those released by Th2 lymphocytes)
– generation of vasodilators such as prostaglandins by inhibiting induction of COX
– activation of eosinophils and other cells
Given by inhalers (not nebulised)
– Main one is beclometasone
In deteriorating asthma oral (e.g. prednisolone) or IV (e.g.
hydrocortisone) can be given.
Cysteinyl-leukotriene receptors antagonists:
Mechanism?
Two receptors?
Target of lukast drugs
Two receptors for cysteinyl-leukotrienes (LTC4, LTD4 and
LTE4) have been cloned (CysLT1 and CysLT2)
– expressed in respiratory mucosa and infiltrating
inflammatory cells
The lukast drugs (e.g. montelukast) antagonise only CysLT1
– ↓ exercise-induced asthma and decrease both early and
late phase responses to allergens
– relax airways in mild asthma
– used mainly as add-on therapy to ICS and LABAs
– ↓ acute reactions to aspirin
Methylxanthines:
- Main drug in use? Mechanism?
- Administration?
- When used as an IV?
Main drug = Theophylline:
- Cyclic nucleotide phosphodiesterase inhibitor
- Increase cyclic nucleotides in the cell to relax smooth muscle
Administration: Oral sustained release formulations used in addition to steroids (e.g. Uniphyllin) in COPD
Rarely used as an IV drug in acute severe asthma
What is the immediate treatment of acute severe asthma?
- Oxygen
- Salbutamol or terbutaline PLUS ipratropium via nebuliser
- IV hydrocortisone or prednisolone tablets
If patient still not recovered:
- IV magnesium sulphate
- Switch from nebulised to IV salbutamol / aminophylline
What is ipratropium?
Uses? (4)
Non-uses? (3)
SAMA Uses: -Patients with COPD -For cough due to irritant stimuli -Decrease mucous secretion and increase clearance of bronchial secretions -Bronchospasm precipitated by b-blockers
Not:
- Uses as an asthma adjunct
- effective against allergen challenge
- selective for one muscarinic receptor
How to construct a well structured clinical question?
E.g. A parent asks whether a single steroid injection would work as
well as five days of oral steroids for their child, John who is about
to be discharged from hospital after an asthma attack. What is
the question you would ask?
Use PICE
- Patient/Population/Problem
- Intervention = Option you are considering
- Comparison = Possible other option
- Outcome = Define the desired outcome
E.g. A parent asks whether a single steroid injection would work as
well as five days of oral steroids for their child, John who is about
to be discharged from hospital after an asthma attack. What is
the question you would ask?
P = Young children I = Single dose of intra-muscular desamethasone C= 5 day treatment with prednisolone O = Resolve the symptoms of asthma
Difference between a null and alternative hypothesis?
Null hypothesis= Two sets of data that are from the same population and not different
Alternative hypothesis = Two sets of data that are from different populations and are different
Two forms of quantitative data?
Discrete: Can only have certain numerical values e.g. Number of children
Continuous: Do not have discrete steps e.g. height and weight
What are the two types of categorical variables?
Nominal (unordered categories)
- Male/female
- Alive/dead
Ordinal (ordered categories)
- Objective: Heavy, moderate or light drinkers (based on no. units of alcohol)
- Subjective: Health status questionnaires
What is the p-value?
Cut off?
The probability that the null hypothesis is correct (meaning the chance there is no difference between the data sets)
An arbitrary cut-off of P> 0.05 has been chosen to indicate that the null hypothesis can be reasonably rejected.
(I.e. low P value means there is a statistically significant difference)
What is a Type I error?
Rejecting the null hypothesis when it’s true (false positive)
Concluding there is an effect when there isn’t (P is small)
Type II error?
Not rejecting the null hypothesis when it is false (false positive)
Concluding there is no effect when there is (P is large)
What is the power of a test?
Its ability to reject the null hypothesis when it is false.
The capacity to detect an effect if there is one present
Sample size is key*
What are the stages of atherosclerotic plaque destabilisation?
Rupture or erosion
Platelet adherence and aggregation
Intracoronary coagulation
Difference between characteristics of an unstable ands stable atherosclerotic plaque?
- Inflammatory cells?
- Fibrous cap?
- No. of smooth muscle cells?
- Endothelium condition?
- Macrophages?
Unstable:
- Inflammatory cells
- Thin fibrous cap
- Few smooth muscle cells
- Eroded endothelium
- Activated macrophages
Stable:
- Lack of inflammatory cells
- Thick fibrous cap
- More smooth muscle cells
- Intact endothelium
- Foam cells
What is cardiogenic shock secondary to?
VSDD
Acute mitral value regurgitation (papillary muscle necrosis)
Acute LV rupture
Ultrasound for the heart, aka…
Echocardiogram
4 complication of an acute MI
- Arryhythmia
- Myocardial death
- LV thrombus and embolization
- Heart failure
Pathology of MI
- Myocyte death
- Coagulation
- Inflammation
- Granulation and scar formation
What are the psychological factors of asthma control?
Association between psychological factors with Asthma related death, near fatal asthma, brittle asthma, non-compliance and A&E visits
Emotions: Depression, anxiety, panic and denial
Cognitive factors. Reduced confidence, beliefs around vulnerability
What is anxiety?
A state of intense apprehension, uncertainty and fear (due to anticipation of a threatening event) to a degree that normal physical and psychological functioning is disrupted
What is anxiety?
A state of intense apprehension, uncertainty and fear (due to anticipation of a threatening event) to a degree that normal physical and psychological functioning is disrupted
Symptoms of anxiety?
Psychological cues e.g. Loss of confidence, sense of dread
Behavioural cues: Fidgeting, hesitating
Cognitive cues: Difficulties with concentration and attention, memory problems
What is effect of coping with anxiety by avoidance?
Good short term (within 3 days)
Long term it leads to more anxiety and depression, reduces physical functions and more discomfort
NOT ADVISED
What are the 3 models of health behaviour used in interpreting asthma psychological factors?
- QoL models: Affect of health condition, environmental factors and personal factors on Body function/structure, activities and participation
- The biomedical model: Physical damage –> Illness
- Biopsychosocial model: Affect of asthma on Biological, Psychological and Social. Assesses overall experience of health and illness
- Leventhal’s Self-regulation model (Common sense model): Looks at how a person makes sense of their condition and the effect of illness representations (beliefs about the condition) on patient
How do you explain the difference in disability between asthma patients?
Emotions: Anxiety, depression
Beliefs and cognitions: Asthma misconceptions, catastrophic thinking
Behaviour: Avoid exercise, excessive rest
Biological: Genetics, bacteria
Social: Limited social support, loss of employment
Psychological factors such as depression, anxiety, fear and panic can
lead to…
Worsening of asthma symptoms and sub-optimal self-management
Self-management of asthma prevents
- Exacerbations
- Improves care
- A cost effective investment for healthcare services
What does the confidence interval represent?
Gives an estimated range of values which is likely to include an unknown population parameter, the estimated range being calculated from a given set of sample data
Describes the uncertainty of the estimate i.e. the range of values within which we can be reasonably sure the true effect lies
Why are confidence intervals more informative than simple results of hypothesis tests?
Confidence intervals are more informative than the
simple results of hypothesis tests since they provide a
range of plausible values for the unknown parameter.
What does the point estimate indicate?
The magnitude of the effect of the experimental intervention compared to the control intervention
Why are confidence intervals better than p values?
- Give a range of possible effect sizes
- Embrace the value of no difference between treatments (not significantly different from the control)
- Help interpret clinical trial data by placing upper and lower bounds on the true effect size
- Statistically significant does not mean clinically
important –the size of the effect determines importance!
3 ways of measuring effectiveness of intervention (e.g. drug)
- Number needed to treat (NNT)
- An NNT is treatment specifc and describes the difference between treatment and control in achieving a particular clinical outcome - Relative risk
- Odd ratio
What is ARR? what is it’s relationship with NNT?
ARR = (no of people benefitted)/ total number of people
NNT is the reciprocal of ARR (opposite)
Probability =
Number of favourable outcomes / total number of possible outcomes
Odd=
Number of favourable outcomes/ number of unfavourable outcomes
How is Relative risk of disease calculated prospectively?
Risk of exposed/risk of not exposed
How is odds of exposure calculated retrospectively?
Odds of exposure in diseased group/off of exposure in no disease group
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Formula for ARR (Absolute risk reduction)
ie risk difference
Risk in unexposed - risk in exposed
Formula for RRR (relative risk reduction)
(1- risk ratio) x 100
Formula for NNT
1/ARR
Formula for NNT
1/ARR
Forest plots: The size of the square is ? The length of the line is the ? The diamond is the ? X-axis scale is logarithmic for \_\_\_ and linear for \_\_\_\_\_\_ Horizontal line is the ? Each square represents an ?
The size of the square is proportional to the study weight
The length of the line is the 95% CI
The diamond is the combined results for all the studies
X-axis scale is logarithmic for ratios and linear for differences
Horizontal line is the line of no effect
Each square represents an individual study
How do you calculate BMI and what are the different categories?
BMI= Mass (kg) / Height ^2 (m)
Normal range = 18.5-24.9 Overweight = 25.0-29.9 Grade I obesity = 30.0-34.9 Grade II obesity = 35.0-39.9 Grade III obesity ≥ 40.0
What do anthropometric measurements look at?
How are the different tests done? 2
Assess body composition (% body fat)
- Skin-fold thickness
Calculate % body fat from skin-fold thickness measurements in mm
Sites: Mid-thigh, subscapular, supra-iliac, triceps
Add all 4 together to produce “sum4” and insert into equation - Measurement of waist and hip circumference
Waist circumference: Hip circumference (mm)
What do anthropometric measurements look at?
How are the different tests done? 2
Assess body composition (% body fat)
- Skin-fold thickness
Calculate % body fat from skin-fold thickness measurements in mm
Sites: Mid-thigh, subscapular, supra-iliac, triceps
Add all 4 together to produce “sum4” and insert into equation - Measurement of waist and hip circumference
Waist circumference: Hip circumference (mm)
How is VO2 max measured?
What is VO2 max?
Calculation?
Good levels for men and women
Standardised step-test
VO2 max= Maximal oxygen uptake capacity in mlO2/kg/min
Calculated by taking pulse immediately after doing steps for 3 minutes. Insert HR into equation
Women = 48-44 Men= 53-45
5 ways to differentiate between JVP and carotid pulse
- JVP has a double waveform
- JVP is impalpable
- JVP obliterated by breathing
- JVP decreases on inspiration
- JVP varies in height with position of patient
What nodes are palpated during the respiratory exam?
Submental Submandibular Occipital Scelene Cervical chains Pre and post auricular
