Joa Joan Sa Salty lty As Asthm hma Kathryn Howell Suraiya - PowerPoint PPT Presentation

Joa Joan Sa Salty lty As Asthm hma Kathryn Howell Suraiya Chowdhury

Ses Session n Ob Object ectives es - Brief overview of receptor pathways - Lung anatomy + histology - Asthma D efinition o R isk factors o D ifferential diagnosis o E pidemiology o A etiology o C linical presentation o P athophysiology o I nvestigations o M anagement o P rognosis o - SBAs - CPH: geographic and temporal studies

Re Receptor or pathways - 4 main families of receptors 1. Ligand-gated receptor/channel complexes 2. G-protein-coupled receptors 3. Tyrosine kinase receptors 4. Intracellular receptors

Re Receptor or pathways REVISION SLIDES: USEFUL A LITTLE LATER IN THE YEAR

Re Receptor or pathways REVISION SLIDES: USEFUL A LITTLE LATER IN THE YEAR

G-pro protein in c coupled re recepto ptors rs G 𝝱 q G 𝝱 S G 𝝱 i (NA at 𝝱 1 adrenoreceptors in blood vessels, (e.g. noradrenaline at β 1- (e.g. Ach at M2 adrenorecptors in the heart vasoconstriction) adrenorecptors in the heart, ↑ HR; ↓ HR β 2-adrenorecptors in the bronchioles, bronchodilation) Activates Phospholipase C, generating IP 3 and Inhibits adenylate cyclase (AC) DAG Stimulates adenylate cyclase (AC) ↓ cAMP levels ↑ cAMP levels IP3 mobilizes Ca2+ from intracellular organelles → Increased cytosolic Ca2+. DAG enhances Protein Kinase ‘C’ activation Inhibits protein kinase A Stimulates protein kinase A by Ca2+.

G-pro protein in c coupled re recepto ptor c r che heat s t she heets ts Q I S S S REVISION SLIDES: USEFUL A LITTLE LATER IN THE YEAR

Thoracic cavity, divided into compartments: Ge Genera ral Anato tomy my • Left pleural cavity • Right pleural cavity • Mediastinum 12 thoracic vertebrae 12 ribs on either side • True ribs: • False ribs: 8-10 th . Cartilage connect to 7 th • Floating ribs: 11 th and 12th Manubrium + body + xiphoid process Diaphragm Separation of thoracis and abdominal cavities Inspiration and expiration Phrenic nerve innervation

Ple Pleura a Visceral = organs Parietal = walls of cavity Thin layer of serous fluid = lubrication and surface tension (facilitates breathing) Pleural recesses (“space”) • Costodiaphragmatic – between costal and diaphragmatic. Clinical important, costophrenic angle to check for pleural effusion on X-ray • Costomediastinal – between costal and mediastinal Parietal pleura : Innervated by phrenic and intercostal nerves. Sensation (pain, temp, pressure) produces well localised pain à referred pain to neck/shoulder) Visceral pleura : Autonomic innervation by pulmonary plexus (network). No sensation EXCEPT stretch Pneumothorax: Air in pleural cavity = loss of surface tension. Mediastinum “pushed” away from side of pneumothorax

Lung Lu ngs Lobes Right has 3 (more letters, more lobes), Left has 2. Formed by: Cone-shaped. Apex + Base + 3 surfaces + 3 borders . • Oblique Fissure – separate inferior from superior+middle. Begins Apex: above 1 st rib T3(L)/4(R), around thorax to level of 6 th rib Base: Diaphragm • Horizontal Fissure – separate superior from middle. Follows 4 th rib, Surfaces: costal, mediastinal and diaphragmatic from inferior borer to posterior border Borders: anterior (sharp), inferior (sharp) and posterior (smooth) Clinical skills: auscultation on right side nipple line to get all lobes Pulmonary artery brings deoxygenated blood from right ventricle Right longer to cross mediastinum. Pulmonary vein brings oxygenated blood to left atrium

Root Root and Hilu lum Lung root : Suspends lungs from mediastinum. Covered by mediastinum pleura Vagus nerve passes posterior to root. Phrenic nerves passes anterior to them Hilum : entry/exit point between root and lungs Within each root and hilum are: • 1 pulmonary artery (superior) • 2 pulmonary veins (inferior) • Main bronchus • Broncial vessels • Nerves • Lymphatics

Trachea Bronchial Br al Tr Tree Flexible tube, C6-T4. Held open by C-shaped cartilage rings, open part on the back. Carina is a full ring circle Cough reflex Pseudostratified ciliated columnar epithelium + goblet cells à mucociliary escalator • innervation: recurrent laryngeal • Inferior thyroid artery Pharynx Bronchi Larynx C3-C6 Each bronchopulmonary segment is a lung segment supplied by its own pulmonary artery. Trachea Carina = T4; bifurcation of trachea 10 in each lung (DON’T LEARN). No cartilage support, only smooth muscle. Right bronchus: shorter, wider, more vertical. FOREIGN OBJECTS Bronchi (1°, 2°, 3°) Bronchioles Bronchioles Terminal bronchioles: Smallest airways. Terminal bronchioles Alveoli Alveolar ducts Simple squamous epithelium. Site of gas exchange Type 1 alveolar cells = alveoli wall, large, flat Alveoli Type 2 alveolar cells = surfactant, proliferate in injury Alveolar macrophages (resident immune cells)

Br Breat athing Diaphragm elevated and depresses. Sternum moves forward and upwards.

As Asthm hma

Th The Pat Patient 25 ♀ landscape gardener - - Presenting complaint 4 month history of coughing and wheezing o chest tightness on exertion o Chest tightness and mild wheeze in cold weather and when mowing the lawn o - Past medical history Eczema and wheezing episodes in childhood o Allergies in summer o - Drugs and alcohol Smokes –10/day, 1-2 joints/week o

Wha What a are t the he d dif ifferentia ial d dia iagnosis is?

Ac Acut ute asthma differential diagnosis Condition Differentiating symptoms Investigations Foreign body/obstruction Localised wheeze, history CXR/bronchoscopy, BDR (no alleviation) Anaphylaxis Stridor (not wheezing), history History Emphysema/COPD Morning or persistent cough/SOB/wheezing*, sputum BDR, spirometry, ** production, history Pulmonary embolism Wheezing unusual, chest pain, history (PE, D-dimer, CTPA, VQ-Scan immobilization, DVT, cancer) Pneumothorax SOB, chest tightness CXR Congestive heart failure Raised JVP, S3 heart sound CXR, BNP, lung crackles USEFUL RESOURECE FOR DDX: BMJ BEST PRACTICE

EPIDEMIOLOGY DEFINITION o 5.4m people in the UK have asthma o Chronic inflammatory conditions o Causes episodic exacerbations of o 1/11 children and 1/12 adults bronchoconstriction i.e. reversible airway o 1,500 deaths per year obstruction and hyper-reactivity. o Approx. 80,000 asthma admissions per o Type 1 hypersensitivity reaction year o Typical triggers include infection, exercise, USEFUL RESOURECES FOR CONDTIONS OVERVIEW: animals, cold/damp, dust, time (at night or - https://zerotofinals.com/ early morning), strong emotions. - https://formedics.co.uk/

Sy Symptoms/Clinical Presentation Episodic symptoms, diurnal variability typically worse at night. Shortness of breath - dyspnoea o Dry cough with wheezing o Chest tightness o History of atopy (e.g. eczema, hay fever, food allergies); family history o Tachycardia o Inability to speak o Sleep disturbance o

Ri Risk factor ors o Genetic component/family history o Exposure to allergens (pollen, dust mites, cigarette smoke) o Atopic history - eczema, atopic dermatitis, allergic rhinitis (hay fever)

Et Etiology

Sens Sensitisation

As Asthmatic response

As Asthma attack - pha phases

Hy Hypersensitivity sum ummar ary You will be taught this later in the year. Just included as revision aid for later. Source: https://www.passmedicine.com/

In Investigations o CXR (normal or hyperinflated) – to rule out other pathologies. o Spirometry (https://geekymedics.com/spirometry-interpretation/) • FEV – forced expiratory volume • FEV 1 – FEV in the first second (improved by bronchodilator – bronchodilator reversibility test) • FVC – forced vital capacity – total amount of exhaled air in 1 breath • FEV1/FVC < 70% predicted in asthma. o Peak expiratory flow rate (PEFR) – fastest you can expel air. Diurnal variation > 15% o FBC - ↑ WCC

Sp Spirometry Obstructive Restrictive FEV 1 ↓ / ↓↓ ↓↓ FVC ↓ /- ↓↓ FEV 1 /FVC ↑ /- ↓

Ma Management

Ch Chronic As Asthma

B2-Agonist (SABA, LABA) Corticosteroids (ICS, OCS) Salbutamol (SABA), Salmeterol (LABA) Beclomethasone (ICS), Prednisolone (OCS) MOA Stimulation of B2 receptors (GaS) on smooth muscle (bronchi, gut, uterus, blood Intracellular effects à cytoplasmic receptors à modify vessels). Bronchodilation transcriptions by interacting with promotor region. Stimulate Na/K ATP pumps = pump K+ into cells to deal with hyperkalaemia. ↓ inflammatory cytokines = reduce mucosal inflammation and secretion Indications 1. Asthma – always with ICS in maintenance of condition 1. Asthma 2. COPD 2. COPD 3. Hyperkalaemia – always with calcium gluconate to stabilise myocardium 4. Premature labour – relax uterine muscle Contraindications Cautions • Given without ICS • Hx of pneumonia COPD Pt • Cardiovascular disease (tachycardia) • Children (growth suppression) • Given with theophylline and ICS à hypokalaemia • Osteoporosis Pt Adverse effects “fight or flight” effects • Oral candidiasis • tachycardia, palpitations, tremor • Hoarse voice • Muscle cramps (LABA) • Irritation