PBL Topic 2 Case 2 Flashcards
What is tidal volume?
- Volume of air inspired or expired with each normal breath
What is inspiratory reserve volume?
- Volume of air that can be inspired over and above the tidal volume
What is expiratory reserve volume?
- Volume of air that can be expired after the end of normal tidal expiration
What is residual volume?
- Volume of air remaining in the lungs after the most forceful expiration
How is inspiratory capacity calculated?
- Tidal Volume + Inspiratory Reserve Volume
How is functional residual capacity calculated?
- Expiratory Reserve Volume + Residual Volume
How is vital capacity calculated?
- Inspiratory Reserve Volume + Expiratory Reserve Volume + Tidal Volume
How is total lung capacity calculated?
- Residual Volume + Vital Capacity
Outline how PEFR is calculated
- Blow out forcefully into the peak flow metre
- Best of three attempts is recorded
- Regular measurements throughout the day
Which condition is PEFR used to diagnose?
- Asthma
What are the normal values of pH?
- 7.35 - 7.45
What are the normal values of PO2?
- 80 - 100 mm Hg
- 10.5 - 13.5 kPa
What are the normal values of PCO2?
- 36 - 45 mm Hg
- 5.1 - 5.6 kPa
What are the normal values of oxygen saturation?
- Between 95% and 100%
Identify two examples of obstructive airways disorders
- COPD
- Asthma
Identify an example of a restrictive airway disorders
- Fibrosis
How can spirometry be used to diagnose an obstructive disorder?
- FEV1 is reduced
- FVC is reduced to a lesser extent than FEV1
- FEV1/FVC ratio < 0.7
How can spirometry be used to diagnose a restrictive disorder?
- FEV1 is reduced
- FVC is reduced approximately the same amount as FEV1
- FEV/FVC ratio > 0.7
Outline Henry’s Law
- Partial Pressure = [Dissolved Gas] / Solubility Coefficient
Explain why the partial pressure of CO2 is much less than that of O2
- CO2 is much more soluble than O2
Why does oxygen diffuse into the blood from the alveoli?
- Partial pressure of oxygen is greater in the gas phase than in the dissolved state
- Movement of oxygen down a pressure gradient
Why does carbon dioxide diffuse into the alveoli from the blood?
- Partial pressure of carbon dioxide is greater in the dissolved state than the gas phase
- Movement of carbon dioxide down a pressure gradient
Outline five factors that affect the rate of gas diffusion
- Partial pressure difference, ΔP
- Cross sectional area, A
- Solubility, S
- Distance, D
- Molecular weight, MW
How does alveolar air differ to atmospheric air?
- Alveolar air has less oxygen than atmospheric air
- Alveolar air has more carbon dioxide than atmospheric air
Outline how alveolar air is replaced by atmospheric air
- Only 1/7 of alveolar air replaced by atmospheric air with each breath
- Improving stability of respiration
- By preventing sudden changes in gas concentrations
Outline the layers of the respiratory membrane
- Alveolar epithelium
- Epithelial basement membrane
- Interstitial space
- Endothelial basement membrane
- Capillary endothelium
What is the value of Va/Q when Va is zero and Q is normal
- Zero
What is the value of Va/Q when Va is normal and Q is zero
- Infinity
What is shunted blood and where does it typically occur?
- Blood that is not oxygenated
- Lower lung
- Where Va/Q = 0
What is physiologic dead space and where does it typically occur
- Alveolar air that is not perfused
- Upper lung
- Where Va/Q is infinity
Outline how Va/Q mismatch alters during exercise
- Blood flow to upper lung increases
- Reduced physiologic dead space
- Va/Q is reduced to an optimum value
Outline how emphysema results in decreased effectiveness of the lungs in relation to Va/Q
- Obstruction results in unventilated alveolar
- Va/Q approaching zero
- Resulting in serious physiologic shunt
- Destruction of alveolar walls results in inadequate perfusion
- Va/Q approaches infinity
- Resulting in serious physiologic dead space
What percentage of oxygen transported from the lungs is carried in combination with haemoglobin?
- 97%
What percentage of oxygen transported from the lungs is carried in the dissolved state in the plasma?
- 3%
Explain how oxygen affinity changes in relation to PO2?
- Where PO2 is high, e.g. in the lungs, oxygen binds with haemoglobin
- Where PO2 is low, e.g. in the tissues, oxygen unbinds from haemoglobin
Explain how haemoglobin is responsible for stabilising PO2
- Tissue requires 5ml of oxygen per 100 ml of blood
- For this to occur, the PO2 must fall to 40 mm Hg
- Therefore, PO2 cannot rise above 40 mm Hg or else not enough oxygen would be released
Identify four factors that cause the oxygen dissociation curve to shift to the right, what is the importance of this?
- Increased acidity
- Increased CO2
- Increased temperature
- Increase 2,3-BPG
- Results in increased oxygen unloading due to the increased metabolic demands of the tissues
Rank the methods by which CO2 is transported in the blood in descending order
- As HCO3- (70%)
- As Hgb.CO2 (23%)
- As CO2 (7%)
Outline how HCO3- is formed from dissolved CO2
- Reacts with water
- Catalysed by carbonic anhydrase
Outline how Hgb.CO2 is formed from dissolved CO2, what is the significance of this bond
- Reacts with amine radicals
- Loose bond allows CO2 to be easily released into the alveoli
What is the Bohr Effect?
- Increase in CO2
- Causes oxygen to be displaced from haemoglobin
What is the Haldane Effect?
- Binding of oxygen with haemoglobin displaces carbon dioxide
What is hypercapnia?
- Excess CO2 in the body fluids
- Initially corrected by pulmonary ventilation
- But eventually depresses respiration
What is Type 1 Respiratory Failure?
- Hypoxia
- Low PCO2
What is Type 2 Respiratory Failure?
- Hypoxia
- Hypercapnia
Define Asthma
- Hyper-reactivity of bronchial tree
- With paroxysmal narrowing
- Which may reverse spontaneously after treatment
What is Status Asthmaticus?
- Asthma whereby symptoms persist for several days
- Leading to respiratory failure and death
Outline the pathogenesis of asthma
- Th2 lymphocytes
- Which facilitate IgE synthesis from IL-4
- And eosinophil inflammation from IL-5
Outline the role of dendritic cells in the pathogenesis of asthma
- Initial uptake of allergens from skin and mucosa
- Presentation to CD4 cells
Outline the role of mast cells in the pathogenesis of asthma
- Exposure to antigen bridges two adjacent IgE molecules on mast cell
- This triggers mast cell to release its mediators
- Primary mediators include histamines, tryptase, prostaglandins and leukotrienes
Outline the role of eosinophils in the pathogenesis of asthma
- Attracted by IL-3, IL-5, GM-CSF and ECF-A
- Release of leukotrienes, major basic protein and eosinophilic cationic protein
What is the effect of cysteinyl leukotrienes in asthma?
- Bronchospasm
What is the effect of eosinophilic cationic protein in asthma?
- Epithelial damage
- Resulting in airway reactivity
- Resulting in bronchospasm
How are cysteinyl leukotrienes activated?
- Metabolism of arachidonic acid
- Via the lipoxygenase pathway
How are prostaglandins activated?
- Metabolism of arachidonic acid
- Via the cyclo-oxygenase pathway
What is the role of ADAM 33?
- Disintegrin and metalloproteinase
- Associated with tissue remodelling
How is the epithelium affected in asthma?
- Loss of ciliated columnar cells
- Metaplasia with an increase in mucous secreting goblet cells
How is the basement membrane affected in asthma?
- Deposition of repair collagens via myofibroblasts
- Thickened basement membrane
How is smooth muscle affect in asthma?
- Hyperplasia of helical bands of airway smooth muscle
- Hyperresponsiveness due to a change in actin-myosin cross-linking cycling
Outline two ways in which neural reflexes contribute to the irritability of asthma
- Central reflexes cause release of acetyl choline stimulates M3 receptors causing contraction
- Local reflexes cause release of neuropeptides causing vasoconstriction
Outline the clinical features of asthma
- Wheezing and shortness of breath
- Made worse at night
Outline the Hygiene Hypothesis
- Components of bacteria, viruses and fungi
- Stimulate toll-like receptors
- Which direct response away from allergic Th2 towards protective Th1
Explain why asthmatics wheeze after exercise or inhaling cold air
- Release of histamines, prostaglandins and leukotrienes from mast cells
- Drying and cooling makes the bronchi hyperosmolar
Explain why asthmatics should avoid NSAIDs
- Inhibit arachidonic acid pathway
- Via the COX-1 pathway
- Prevent synthesis of prostaglandins
- Thus increasing production of leukotrienes
Explain why asthmatics should avoid beta-blockers
- Blockage of B2-adrenoreceptors
- Leads to bronchoconstriction and airflow limitation
Identify five other precipitating factors in asthma
- Occupational molecular weight compounds
- Atmospheric pollution and irritants
- Vapours an fumes
- Diet
- Emotional factors
Outline the reversibility test for asthma
- Inhalation of bronchodilator or use of corticosteroid
- Results in at least a 15% increase in FEV1
- Diagnosis of asthma
Outline the exercise test for asthma
- Run on a treadmill for 6 minutes at a speed that produced over 160 bpm
- Results in at least a 15% decrease in FEV1
- Diagnosis of asthma
What may a chest x-ray show in asthma?
- Overinflation
Outline two examples of a short acting B2 adrenoreceptor agonist, how they are given and their duration of action
- Salbutamol
- Terbutaline
- Inhalation, as and when
- 3-5 hours
Outline two examples of a long acting B2 adrenoreceptor agonist, how they are given and their duration of action
- Salmeterol
- Formoterol
- Inhalation, regularly
- 8-12 hours
Outline the mechanism of action of B2 adrenoreceptor agonists
- Bind to B2-adrenoreceptor
- Adenylate Cyclase cAMP second messenger system
- Bronchodilation
Outline two other effects of B2 adrenoreceptor agonists
- Inhibit mediator release from mast cells
- Inhibit TNF-a release from monocytes
- Increase mucous clearance by action of cilia
Explain why B2 adrenoreceptors may cause tremor
- Increase in muscle spindle discharge
- Coupled with an effect on the contraction kinetics of the fibres
Explain why B2 adrenoreceptors may cause tachycardia
- Vasodilation reduced venous return and thus reduces cardiac output
- Also act as B1 agonists so increase heart rate by SA node
- V
Explain why B2 adrenoreceptors may cause dysrhythmias
- Hypokalaemia
- Caused by an increased uptake of K+ by skeletal muscle
Outline one example of a xanthine drug
- Theophylline
Outline the mechanism of action of xanthine drugs
- Inhibition of phosphodiesterase enzymes, with resultant increase in cAMP (and thus bronchodilation)
- Competitive antagonism of adenosine A1
- Activates histone deacetylase, reversing resistance to the anti-inflammatory effects of corticosteroids
Identify four adverse effects of xanthine drugs
- Insomnia
- Nervousness
- Cardiac dysrhythmias
- Seizures
Identify an example of a muscarinic receptor antagonist
- Ipratropium
Outline the mechanism of action of muscarinic receptor antagonists
- Inhibition of M3 receptors which cause smooth muscle contraction
Explain why rifampicin reduces plasma concentration of theophylline
- Theophylline is metabolised by P450 enzymes
- Rifampicin induces P450 enzymes
Explain why erythromycin increases plasma concentration of theophylline
- Theophylline is metabolised by P450 enzymes
- Erythromycin inhibits P450 enzymes
How are xanthine drugs such as theophylline given?
- Orally
How are muscarinic receptor antagonists given?
- Aerosol inhalation
What is the duration of action of muscarinic receptor antagonists?
- 3 -5 hours
Identify an example of a cysteinyl leukotriene receptor antagonists
- Montelucast
Outline the mechanism of action of cysteinyl leukotriene receptor antagonists
- Inhibition of CysLT1 and CystLT2 receptors
- Prevent binding of LTC4 and LTD4
- Inhibiting bronchospasm and mucous secretion
Identify two adverse effects of cysteinyl leukotriene receptor antagonists
- Headache
- GI disturbances
What is the mechanism of action of Omalizumab?
- Anti-inflammatory
- Anti-IgE antibody
Outline the mechanism of action of glucocorticoids in asthma in relation to cytokines
- Decreased formation of Th2 cytokines
- Such as IL-4 that promotes production of IgE
- And IL-5 that promotes activation of eosinophils
Outline the mechanism of action of glucocorticoids in asthma in relation to vasodilators
- Inhibit PGE2 and PGI2 by inhibiting the induction of COX-2
- Inhibit leukotrienes and PAF by inducing annexin-1
Outline the main glucocorticoids used in asthma treatment
- Beclometasone
- Or a higher potency Budesonide
Outline the glucocorticoids used in acute exacerbations of asthma
- Intravenous hydrocortisone
- Oral prednisolone
Identify three adverse effects of glucocorticoids
- Oral candidiasis
- Sore throat
- Croaky voice
Outline the pathological basis of clear sputum
- Excess secretion from bronchial mucous glands
Outline the pathological basis of purulent sputum
- Inflammatory exudate from respiratory tract infection
Outline the pathological basis of haemoptysis
- Ulceration of airways or damage to pulmonary vasculature
Outline the pathological basis of cough
- Physiological reflex response to mucous, exudate, tumour or foreign material
Outline the pathological basis of wheezing on inspiration (stridor)
- Narrowing of larynx, trachea or proximal bronchi (tumour)
Outline the pathological basis of wheezing on expiration
- Narrowing of distal bronchi (asthma)
Outline the pathological basis of cyanosis
- Increased non-oxygenated blood e.g. by impaired gas exchange
Outline the pathological basis of pleuritic pain
- Irritation of pleura due to inflammation, infarction or tumour
Outline the pathological basis of transudate pleural effusion
- A high protein effusion
- Seen in heart failure
Outline the pathological basis of exudate pleural effusion
- A low protein effusion
- Seen in inflammation or tumours
Outline four pathological bases of finger clubbing
- Lung carcinoma
- Bronchiectasis
- Pulmonary fibrosis
- Cirrhosis
Outline the pathological basis of weight loss
- Protein catabolic state
- Induced by chronic inflammatory disease or tumour
Outline the pathological basis of crackles on auscultation
- Sudden inspirational opening of small airways resisted by fluid or fibrosis
Outline the pathological basis of wheezes on auscultation
- Generalised or localised airway narrowing
Outline the pathological basis of pleural rub on auscultation
- Pleural surface roughened by exudate
Outline the pathological basis of dullness on percussion
- Consolidation of lung by exudate
- E.g. pneumonia
Outline the pathological basis of hyper-resonance on percussion
- Increased gas content of thorax
- E.g. pneumothorax or emphysema
What is meant by the term agonist?
- A drug that binds to receptor and activates it
What is meant by the term antagonist?
- A drug that binds to a receptor and prevents an agonist binding to and activating it
What is meant by the term affinity?
- The tendency of a drug to bind to a receptor
What is meant by the term efficacy?
- The tendency of a drug to activate a receptor once bound
What is meant by the term partial agonist?
- A drug with partial efficacy
- (Such that even 100% of receptors are occupied the response is sub-maximal)
What is meant by the term inverse agonist
- A drug that binds to a receptor and causes negative efficacy
How does efficacy differ in agonists, antagonists and inverse agonists
- Agonist: Positive
- Antagonist: Neutral
- Inverse Agonist: Negative
What is the difference between Emax and EC50/ED50
- Emax is the maximal response a drug can produce
- EC50/ED50 is the concentration/dose needed to produce 50% of the maximal response
Explain why physiological response is not directly proportional to receptor occupancy by an agonist
- Enzyme degradation or rapid uptake by cells
How does a competitive antagonism differ to other types of antagonism?
- Effects are surmountable
- Meaning they can be overcome by increasing concentration of agonist
Identify three other types of antagonists
- Chemical antagonism (two substances combine in solution, effect of drug lost)
- Pharmacokinetic antagonism (antagonist reduces absorption, metabolism or excretion of drug )
- Physiological antagonism (two agents produce opposing physiological effects).
According to Ley’s Model of compliance, what factors influence compliance?
- Understanding
- Memory
- Satisfaction
According to Ley, how can clinicians improve compliance via oral information?
- Stress the importance of compliance
- Simplify information
- Use repetition
- Follow up consultation with additional interviews
- Primary effect (patients remember first thing they are told)
What is psychosomatic illness?
- Physical symptoms are produced by actions of the unconscious mind
Identify the two forms of psychosomatic illness
- No lesion of any kind and symptoms are literally psychogenic
- Organic lesion exists though patient response is exaggerated
Explain why general practice has a key role in management of psychosomatic illness?
- At least 20% to 30% of primary care patients have medically unexplained symptoms
What should medical care of medically unexplained symptoms include?
- Improvements in communication, diagnosis and specific treatment strategies
Identify how medically unexplained symptoms can be treated, and the limitations of this treatment
- Cognitive Behavioural Therapy
- Lack of availability
What is meant by the term compression?
- Patients overestimate low risks and underestimate high risks
What is mean by the term miscalibration?
- Patients overestimate the accuracy of their own knowledge
What is meant by the term availability?
- Patients overestimate notorious risks
What is meant by the term optimism?
- Patients underestimate their susceptibility
