Respiratory Medicine Flashcards

Question

Summary of the main effects of the parasympathetic NS on the body?

Answer 1

Activation of the parasympathetic nervous system.... - Reduces heart rate - Increases glandular secretion - Increases peristalsis and relaxes sphincters in the gastrointestinal tract - Supports emptying of the bladder - Constricts the pupil

Answer 2

Activation of the sympathetic nervous system... 1. Raises blood pressure 2. Increases heart rate 3. Preserves extracellular fluid volume 4. Mobilises energy stores 5. Inhibits many of the housekeeping functions of the parasympathetic system

Answer 3

Resistance to airflow is controlled at the bronchiole level The most important influence on airway diameter and resistance is the tone of the smooth muscle around the bronchi and bronchioles Fight between factors that drive contraction and dilatation - many drugs try to influence this balance The main factor favouring **contraction** is the parasympathetic nervous system - post-ganglionic fibres secrete the neurotransmitter acetylcholine which acts at muscarinic M3 receptors on bronchial smooth muscle and glandular cells, and mediate bronchoconstriction and mucus secretion - main driver at rest During inflammation - leukotrienes and histamine are released driving contraction The main factor favouring **dilatation** is the sympathetic nervous system via circulating adrenaline released from the adrenal glands and acting at beta-2 adrenoceptors located on bronchial smooth muscle. This mechanism is a minor influence at rest but becomes more important during exercise or the stress response to acute bronchospasm during asthma exacerbations

Answer 4

Bronchodilators are, by definition, drugs that increase the diameter of the respiratory airways by relaxing the layer of smooth muscle surrounding the bronchi and bronchioles - reduces the resistance to airflow and the work of breathing. Important two... **Beta-2 agonist drugs** activate beta-2 adrenoceptors found on the surface of bronchial smooth muscle cells that are the physiological target of circulating catecholamines such as adrenaline - divided into... a) Short duration of action (e.g. salbutamol, terbutaline) b) Longer-acting (e.g. salmeterol, formoterol). **Anti-muscarinic drugs** activate muscarinic M3 receptors that are the physiological target of the neurotransmitter acetylcholine a) Short duration of action (e.g. ipratropium bromide) b) Longer-acting (e.g. tiotropium, aclidinium bromide). Note - Phosphodiesterase inhibitors target the enzyme phosphodiesterase (PDE) that is responsible for the breakdown of cyclic adenosine monophosphate (cAMP), which is a secondary messenger for beta-2 adrenoceptors

Answer 5

Rationale - Drug delivered directly to its site of action - Limited collateral effects on other tissues Inhaler devices are used - Metered-dose inhaler (MDI) - requires a certain levels of technique/coordination - spacer device is an alternative - Dry powder inhaler (DPI) - Mechanical Nebulizer devices – drug put into a container which is driven in by airflow/O2 – used in emergency situations Note - Size of aerosolized is important – 2.5 microns to reach site of action

Answer 6

Adverse effects due to localisaiton of Beta-2 receptors on other tissues like muscles, heart, etc - interfer with contractions

Answer 7

Used for COPD – helps to reduce glandular secretion – big problem in COPD patients Anti-cholinergic side effects are important to learn – classic group of adverse effects – inhibition of PS NS action Glaucoma - eye conditions related to optic nerve damage

Answer 8

Phosphodiesterase inhibitors – prevent the breakdown of cAMP – increasing its ability to activate PKA and thus preventing contraction driven by MLC kinase Adverse side effect – similar to the potentiation of B2 receptor – acting on the same system

Answer 9

Small print stuff Smooth muscle relaxant Last stage drug used – acute severe bronchospasm

Answer 10

Inhibit the activity of leukotrines - prevents smooth muscle contraction, decreases immune chemotaxis and decrease vascular permeability

Answer 11

Corticosteroids used as a preventer measure – reduce airway inflammation in asthma and COPD Pathophysiology in asthma and COPD - airways inflammation - bronchoconstriction - excessive mucous secretion Either use... 1. Inhaled corticosteroids (e.g. beclometasone, budesonide) - administered daily/preventative medication - inhalation allows targetted effects, while minimising systemic impact 2. Systemic corticosteroids are used for more acute exacerbations - prednisolone PO or hydrocortisone IV

Answer 12

SABA - short acting beta agonist ICS - inhaled corticosteroid LRTA - Leukotrine receptor antagonist LABA - long acting beta agonist LAMA - Long-acting muscarinic antagonists

Answer 13

Examples: Inhaled: beclometasone, fluticasone Oral: hydrocortisone, prednisolone IV/IM: hydrocortisone, methylprednisolone, dexamethasone Topical: hydrocortisone, betamethasone Mechanism of action - Bind to intracellular receptors to alter translation of DNA - Macrophages and T cells are key cell targets in inflammation Indications - inflammatory diseases such as asthma, COPD exacerbations, RA, etc. - allergic emergencies, adrenal insufficiency Adverse effects - Wide range of effects including osteoporosis, weight gain, diabetes, susceptibility to infeciton, muscle wasting (myopathy), dyspepsia, psychosis and hypertension

Answer 14

1. Beta blockers (drive bronchoconstriction) - never given to patients with troublesome asthma - block activity of beta-2 receptor – note even though Beta-1 antagonists are selective there is overlap! 2. NSAIDS – stop prostaglandin production - interference with COX drives increases leukotrine production - promoting bronchoconstriction and inflammation 3. Cholinesterase inhibitors - increase pool of ACh resulting in increase M3 activity and thus bronchoconstriction 4. Beta-2 agonists (paradoxical bronchospasm) - phenomenon that is sometimes observed

Answer 15

Large number of drugs that have been associated with lung inflammation (pneumonitis) and progression to fibrotic scarring (pulmonary fibrosis) - drugs that have been associated with interstial lung disease. Antibiotics - nitrofurantoin Anti-rheumatic drugs - methotrexate, sulfasalazine - Biological agents - adalimumab, etanercept Cancer chemotherapy Cardiovascular drugs - amiodarone Ergot derivatives - methysergide, bromocriptine, cabergoline

Answer 16

Examples of drugs that have direct inhibitory effects on the respiratory centre and chemoreceptors that drive breathing Hypnotics - promote sleep Drugs that cause paralysis - paralysis of respiratory musculature

Answer 17

The term ‘particulates’ relates to the exposure to a dry aerosol composed of separate particles which are themselves scientifically defined as very small pieces of solid matter. Basically... very small particles, which when the body is exposed to can have numerous health implications The risk of disease resulting from particles is largely composed of the inherent toxicity of a particle (hazard) and the level of exposure RISK = HAZARD X EXPOSURE

Answer 18

Nanoparticles cause more inflammation than the same mass of fine respirable particles composed of the same material

Answer 19

Nanoparticles have one or more dimensions less than 100nm

Answer 20

In the alveolar region there is no cilia – can’t mechanically move things out – instead the body relies on the immune system, especially macrophages, to remove foreign bodies

Answer 21

Inhalable fraction – the mass fraction of total airborne particles which is inhaled through the nose and mouth. Extrathoracic fraction – the mass fraction of inhaled particles failing to penetrate beyond the larynx. Thoracic fraction – the mass fraction of inhaled particles penetrating beyond the larynx. Respirable fraction – the mass fraction of inhaled particles penetrating to the unciliated airways.

Answer 22

Diameter is important as it dictates how a particle acts in airflow - influence a particles ability to penetrate and deposit in the lungs Large particles settle higher in the airway, compared to smaller particles A lot of forces involved - airflow, diffusion, electrostatic, etc.

Answer 23

Yes, particles can move around to other tissues – e.g. liver and spleen

Answer 24

Lower respiratory tract - lack of cilia Hence, macrophages can engulf the particles and migrate to the lymph node or move up to the mucocilliary escalator to be pushed out the lung Anything larger than 10microns – difficult to phagocytose for macrophage

Answer 25

Fibres are defined as having a length greater than 5µm, a diameter less than 3µm and a length to width ratio of greater than 3:1 Naturally Occurring 1. Asbestos 2. Pele’s Hair 3. Plant Fibres (e.g. Cotton) Man-Made: 1. Insulation wools 2. Refractory Ceramic Fibres 3. Silicon Carbide 4. Carbon Nanotubes

Answer 26

Fibres are defined as having a length greater than 5µm, a diameter less than 3µm and a length to width ratio of greater than 3:1 Naturally Occurring 1. Asbestos 2. Pele’s Hair 3. Plant Fibres (e.g. Cotton) Man-Made: 1. Insulation wools 2. Refractory Ceramic Fibres 3. Silicon Carbide 4. Carbon Nanotubes

Answer 27

Fiber doesn’t tumble – travels straight as a arrow/javelin Movement up and down as it travels – will dictate the length down the lung it reaches - determined by fibres physical diameter not length

Answer 28

Fibre Pathogenicity Paradigm They are thin, bio-persistent (doesn't breakdown/resistant to acidification) and long

Answer 29

Start to produce proteolytic enzymes and low pH – because this vesicle is open it will be released into the surroundings – resulting in excessive inflammation

Answer 30

Yes, movement into pleural space is possible – drains present (stomata) in the pleural space to drain debris/dead cells. This allows some of the small fibres to be moved out, but fibres that are too large build up if they can’t be filtered out - irritating/inflammation of the mesothelium

Answer 31

The ability to persist in the biological environment is a key attribute of a pathogenic fibre

Answer 32

Pleural mesothelioma Pleural plaques

Answer 33

**OBSTRUCTIVE DISORDER** - A disorder in which the radius of an airway is narrowed, thus reducing airflow in and out of the lungs (can be trachea, bronchi, bronchioles, etc.) **RESTRICTIVE DISORDER** - A disorder in which prevents normal expansion of the lungs

Answer 34

**Extra-pulmonary disease** - extra-pulmonary tissues effected - visceral pleura, pleural space, chest wall including parietal pleura, bones, muscles, nerves **Intra-pulmonary disease** - intra-pulmonary tissues effected - i.e. alveoli and surrounding lung tissue (=parenchyma)

Answer 35

1. Integrity of nerves to respiratory muscles e.g. high cervical dislocation 2. Impaired neuromuscular junctions e.g. myasthenia gravis 3. Impaired muscles e.g. muscular dystrophy 4. Pleural thickening - e.g. asbestos exposure, TB, haemothorax, etc 5. Skeletal abnormalities e.g. scoliosis

Answer 36

Lung and chest wall are elastic 1. Lungs natural tendency deflate 2. Chest wall has a natural tendency to inflate Difference in chest wall and lung elastic pressure is called the transpulmonary pressure To inflate the lung we need to overcome the transpulmonary pressure (equilibrium) but either increase thoracic volume (normal breathin) in order to decrease pleural and alveolar pressure OR we could apply an inflation pressure (ICU setting) Image uses the diagram alveoli as a conceptual framework for the lung

Answer 37

Fibrotic lung/alveoli a) Decreased compliance means that an increased pressure is required to inflate the lung - restricts inflation b) Increased elastic recoil does mean that deflation is easier Typical of **fibrotic lung disease**

Answer 38

Lung that is increasingly compliance Decreased elastic tissue and increase complianced makes it... a) Easier to inflate - less resistance b) Difficult to deflate - less elastic tissue and recoil **Typical of emphysema**

Answer 39

Inward force generated by fluid layer surface tension (sT) Force created by fluid lining the alveoli is dependant on the radius and shape of the alveoli: a) Smaller radius - increased force b) Bigger radius - decreased force Hence, given that the inflationay pressure is constant - the total alveolar pressure (pressure driving collapse) will be larger in smaller alveoli.

Answer 40

Consequence - air will move from HIGH pressure area to LOW pressure areas Small alveoli with higher pressure - empty in larger alveoli with lower pressures - resulting in **instability**

Answer 41

Surfactant Produced by alveolar Type II cells - reduces surface tension Composed of lipids (90%, mainly phospholipids) and proteins (10%)

Answer 42

Surfactant molecules act to reduce surface tension but only when they are close togther Hence.... 1. In large alveoli or in expanded lungs - the surfactant only minimally reduces surface tension - minimal impact of pressure 2. In small alveoli or in in delated lungs - the surfactant significantly reduces surface tension - resulting in reduced alveolar pressure Net result - equalises pressure between adjacent alveoli or differing sizes - removing alveolar instability

Answer 43

Disease caused by a lack of surfactant - Alveolar collapse and instability lead to hypoxia and increased work of breathing

Answer 44

Primary surfactant deficiency is very rare in adult disease, but impaired surfactant biology probably contributes to the pathogenesis of common respiratory disorders……. For example... 1. Adult respiratory distress syndrome (ARDS) 2. Pneumonia 3. Idiopathic pulmonary fibrosis 4. Lung transplant

Answer 45

**Obstructive** - FEV1 reduced but FVC normal (exceptions in severe obstruction) – ratio decreased - TLC (total lung capacity) increased and VC (vital capacity) decreased **Restrictive** - FEV1 may be reduced and FVC will almost always be reduced – ratio is normal or elevated – change in FEV1 is usually smaller than FVC change - TLC (total lung capacity) and VC (vital capacity) are decreased

Answer 46

Nope! Spirometry and lung volumes are identical in both cases!

Answer 47

Look at Gas Transfer Measurements This entails looking at... a) GAS EXCHANGE - use low levels of carbon monoxide (CO) - rapidly taken up by hemoglobin/high affinity, not produced by the body, not toxic and easy to measure b) ALVEOLAR VOLUME - use helium gas - not taken up by hemoglobin, not produced by the body, non-toxic and easy to measure.

Answer 48

Breathing in and out of a container with a known conc. of Helium and CO, until the subject reaches a steady state Reduction in the volume of the container corresponds to the volume of air in the alveoli (alveolar volume) - note the tube connecting (tubing volume) is subtracted Decrease in CO after reaching steady state – indicates gas transfer – amount of CO taken up into the lungs – total CO exchange capacity Va = Alveolar volume = number of contributing lung units TLCO (mmol/min/kPa) =Total CO exchange capacity We can get the measure the efficiency of gas transfer per unit lung, known as KCO, is equal to TLCO/Va

Answer 49

Looking at both alveoli and bood vessels Extra pulmonary - **TLCO is low but KCO is normal/high** - normal alveoli + blood supply – total transfer of CO is reduced as lung is reduced in size/in-cased in a smaller area but each blood supply is normal or high (increase packing of blood vessels with alveoli) Intra-pulmonary – **TLCO and KCO are both low** – lungs are smaller and alveoli are diseased and damaged – alveolar unit has an impaired ability to transfer gas KCO looks at gas transfer, so it makes sense that is is lower in fibrotic/intra-thoracic restrictive diseases KCO – is the distinguishing factor between intra and extra-thoracic restrictive diseases!

Respiratory Medicine Flashcards

(80 cards)