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
• Definition
• Risk factors
• Differential diagnosis
• Epidemiology
• Aetiology
• Clinical presentation
• Pathophysiology
• Investigations
• Management
• Prognosis
• SBAs
• CPH: geographic and temporal studies

Re Receptor

• r 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

• r pathways

REVISION SLIDES: USEFUL A LITTLE LATER IN THE YEAR

Re Receptor

• r pathways

REVISION SLIDES: USEFUL A LITTLE LATER IN THE YEAR

G-pro protein in c coupled re recepto ptors rs

G𝝱S (e.g. noradrenaline at β1- adrenorecptors in the heart, ↑ HR; β2-adrenorecptors in the bronchioles, bronchodilation) Stimulates adenylate cyclase (AC) ↑ cAMP levels Stimulates protein kinase A G𝝱i (e.g. Ach at M2 adrenorecptors in the heart ↓HR Inhibits adenylate cyclase (AC) ↓ cAMP levels Inhibits protein kinase A G𝝱q (NA at 𝝱1 adrenoreceptors in blood vessels, vasoconstriction) Activates Phospholipase C, generating IP3 and DAG IP3 mobilizes Ca2+ from intracellular

• rganelles → Increased cytosolic Ca2+.

DAG enhances Protein Kinase ‘C’ activation by Ca2+.

G-pro protein in c coupled re recepto ptor c r che heat s t she heets ts

REVISION SLIDES: USEFUL A LITTLE LATER IN THE YEAR Q I S S S

Ge Genera ral Anato tomy my

Thoracic cavity, divided into compartments:

• Left pleural cavity
• Right pleural cavity
• Mediastinum

12 thoracic vertebrae 12 ribs on either side

• True ribs:
• False ribs: 8-10th. Cartilage connect to 7th
• Floating ribs: 11th 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

Lu Lung ngs

Cone-shaped. Apex + Base + 3 surfaces + 3 borders. Apex: above 1st rib Base: Diaphragm Surfaces: costal, mediastinal and diaphragmatic Borders: anterior (sharp), inferior (sharp) and posterior (smooth) Pulmonary artery brings deoxygenated blood from right ventricle Right longer to cross mediastinum. Pulmonary vein brings oxygenated blood to left atrium Lobes Right has 3 (more letters, more lobes), Left has 2. Formed by:

• Oblique Fissure – separate inferior from superior+middle. Begins

T3(L)/4(R), around thorax to level of 6th rib

• Horizontal Fissure – separate superior from middle. Follows 4th rib,

from inferior borer to posterior border Clinical skills: auscultation on right side nipple line to get all lobes

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

Br Bronchial al Tr Tree

C3-C6 Carina = T4; bifurcation of trachea Right bronchus: shorter, wider, more vertical. FOREIGN OBJECTS

Pharynx Larynx Trachea Bronchi (1°, 2°, 3°) Bronchioles Terminal bronchioles Alveolar ducts Alveoli

Trachea 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

Bronchi Each bronchopulmonary segment is a lung segment supplied by its own pulmonary artery. 10 in each lung (DON’T LEARN). No cartilage support, only smooth muscle. Bronchioles Terminal bronchioles: Smallest airways. Alveoli Simple squamous epithelium. Site of gas exchange Type 1 alveolar cells = alveoli wall, large, flat 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
• chest tightness on exertion
• Chest tightness and mild wheeze in cold weather and when mowing the lawn
• Past medical history
• Eczema and wheezing episodes in childhood
• Allergies in summer
• Drugs and alcohol
• Smokes –10/day, 1-2 joints/week

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 production, history BDR, spirometry, ** Pulmonary embolism Wheezing unusual, chest pain, history (PE, immobilization, DVT, cancer) D-dimer, CTPA, VQ-Scan Pneumothorax SOB, chest tightness CXR Congestive heart failure Raised JVP, S3 heart sound CXR, BNP, lung crackles

USEFUL RESOURECE FOR DDX: BMJ BEST PRACTICE

DEFINITION

• Chronic inflammatory conditions
• Causes episodic exacerbations of

bronchoconstriction i.e. reversible airway

• bstruction and hyper-reactivity.
• Type 1 hypersensitivity reaction
• Typical triggers include infection, exercise,

animals, cold/damp, dust, time (at night or early morning), strong emotions.

EPIDEMIOLOGY

• 5.4m people in the UK have asthma
• 1/11 children and 1/12 adults
• 1,500 deaths per year
• Approx. 80,000 asthma admissions per

year

USEFUL RESOURECES FOR CONDTIONS OVERVIEW:

• https://zerotofinals.com/
• https://formedics.co.uk/

Sy Symptoms/Clinical Presentation

Episodic symptoms, diurnal variability typically worse at night.

• Shortness of breath - dyspnoea
• Dry cough with wheezing
• Chest tightness
• History of atopy (e.g. eczema, hay fever, food allergies); family history
• Tachycardia
• Inability to speak
• Sleep disturbance

Ri Risk factor

• rs
• Genetic component/family history
• Exposure to allergens (pollen, dust mites, cigarette smoke)
• 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

• CXR (normal or hyperinflated) – to rule out other pathologies.
• Spirometry (https://geekymedics.com/spirometry-interpretation/)
• FEV – forced expiratory volume
• FEV1 – 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.
• Peak expiratory flow rate (PEFR) – fastest you can expel air. Diurnal variation > 15%
• FBC - ↑ WCC

Sp Spirometry

Obstructive Restrictive FEV1 ↓↓ ↓/↓↓ FVC ↓/- ↓↓ FEV1/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 vessels). Bronchodilation Stimulate Na/K ATP pumps = pump K+ into cells to deal with hyperkalaemia. Intracellular effects à cytoplasmic receptors à modify transcriptions by interacting with promotor region. ↓ inflammatory cytokines = reduce mucosal inflammation and secretion Indications 1. Asthma – always with ICS in maintenance of condition

• 2. COPD
• 3. Hyperkalaemia – always with calcium gluconate to stabilise myocardium
• 4. Premature labour – relax uterine muscle

1. Asthma

• 2. COPD

Contraindications Cautions

• Given without ICS
• Cardiovascular disease (tachycardia)
• Given with theophylline and ICS à hypokalaemia
• Hx of pneumonia COPD Pt
• Children (growth suppression)
• Osteoporosis Pt

Adverse effects “fight or flight” effects

• tachycardia, palpitations, tremor
• Muscle cramps (LABA)
• Oral candidiasis
• Hoarse voice
• Irritation

Leukotriene receptor antagonists (LTRA) Muscarinic antagonist

Montelukast Ipratropium, Theophylline (LAMA)

MOA

Block the activation of leukotriene receptors (CysLT1) à inhibit inflammatory mechanisms Reduce inflammation and bronchoconstriction Bind muscarinic receptors, competitive inhibitor of Ach = reduce smooth muscle tone, reduce secretion (resp and bladder), relax pupillary constrictor (dilation) and ciliary muscle

Indications

• 1. Add-on therapy Asthma
• 2. Alternative to LABA for 5-12yrs
• 3. 1st line prevention for under 5yrs (cannot take ICS)
• 1. COPD
• 2. Asthma – short-acting in attack, LAMA for prevention

Contraindications Cautions

Only use if asthma is uncontrolled.

• Pregnancy
• Closed-angle glaucoma
• Arrhythmias
• Urinary retention

Adverse effects

• Headache
• Abdo pain
• Churg-strauss syndrome
• Irritation
• GI disturbances (constipation)
• Blurred vision
• Headaches

As Asthma

Ac Acut ute As Asthma

Initial presentation O SHIT

• Oxygen
• Salbutamol 5mg
• Hydrocortisone 100mg/ Prednisolone 50mg
• Ipratropium bromide

Order chest X-ray No sedatives Life-threatening asthma?

• Call senior team HELPPPPPPP
• IV magnesium sulphate IV over 20 mins
• More salbutamol – every 15-30 mins or

10mg over an hour Pt improving

• Continue O2
• Prednisolone daily or hydrocortisone 6hrly
• B2 agonist + ipratropium 6hrly

Pt not improving

• Continue O2 and steroids
• Salbutamol 15-30mins
• Ipratropium 6hrly

Pt still not improving

• Call for HELP
• IV magnesium sulphate over 20mins
• IV B2 agonists or IV aminophylline. Only

senior consultant

• Potential need for ventilation to protect

against type 2 respiratory failure

Monitoring

• Repeat PEF every ~30mins after treatment

started

• O2 stats; maintain >94%
• ABGs within 1 hr of starting treatment

(monitor for respiratory failure)

• Chart PEF before and after B2 agonist and

at least 4 times daily during hospital stay

Discharge

• On discharge meds for 12-24hrs
• Inhaler check
• PEF >75% of best and PEF diurnal variability

<25%

• Prescribe oral steroids (prednisolone) for at least

5 days

• ICS added to treatment plan
• Own PEF + asthma action plan
• GP within 2 working days
• Resp clinic within 4 weeks

Transfer?

• If deteriorating PEF

, hypoxia or hypercapnia need to transfer to ICU

• Exhaustion, altered consciousness

(WHAT ARE WE WORRIED ABOUT HERE?)

Re Respirator

• ry Failu

lure

pO2 less than 8kPa No signs of hypercapnia pO2 <8kpa pCO2 <6.5kpa Hypercapnia (high CO2) pO2 <8kpa pCO2 >6.5kpa

Type 1 respiratory failure

Caused by a Ventilation: perfusion disruption (V/Q mismatch) Air flowing in and out is not matching blood flow to lungs. Shunts, altitude, asthma, COPD, MI Caused by ventilation failure Inadequate alveoli ventilation affecting CO2 and O2 levels COPD, life-threatening asthma,

Type 2 respiratory failure

AB ABG

@gradmedtips https://abg.ninja/abg

Qu Questio stions? s?

SB SBAs

An 8-year-old boy is diagnosed with asthma. His mother asks you what is causing her child's symptoms. Which of the following is the best response

A. Reversible inflammation of the lining of the small airways causing them to become narrower B. Chronic inflammation of the lining of the small airways causing them to become narrower C. Scar tissue formation within the lungs making inflation difficult D. Mucus that is stickier than it should be causing blocked airways E. Infection of the airways causing them to become narrower

A 10-year-old boy is referred to a respiratory physician for persistent bouts of shortness of

• breath. He also has severe hay fever and eczema. He undergoes a peak expiratory flow test,

which suggests signs of outflow obstruction of his lungs. He is trialled on beclomethasone and salbutamol. The physician also informs the mother that he should be kept away from dust, as asthma is a condition that commonly arises from hypersensitivity to dust. Which hypersensitivity is asthma associated with?

A. Type 1 Hypersensitivity B. Type 2 Hypersensitivity C. Type 3 Hypersensitivity D. Type 4 Hypersensitivity E. Type 5 Hypersensitivity

Spirometry of an asthmatic patient would show:

A. Decreased FVC B. Increased FEV1/FVC C. Less than 70% normal FEV1/FVC D. Normal FEV1 E. Increased FVC

A patient has a spirometry test. He has a reduced FEV1/FVC. What condition is this characteristic of? A. Pleural effusion B. Pulmonary embolism C. Chronic obstructive pulmonary disease D. Pulmonary fibrosis E. Kyphoscoliosis.

A 25-year-old lady, who was diagnosed with eczema and asthma in childhood, attends her annual asthma review. Over the past 3 months, she has frequently required her salbutamol reliever. She is worried that the deterioration in asthma control coincides with the adoption of a kitten. In the pathophysiology of allergic asthma which cell is found in inappropriately increased numbers?

A. Mast cells B. Eosinophils C. Dendritic cells D. Macrophages E. Neutrophils

Wh Which of f these is not true ue of f as asthma? a?

A. Airway may show reversible changes during attack B. FEV1 and FVC are reduced by the same amount C. Spirometry may be normal D. Is an obstructive disease

As As outlined ned by by BTS gu guidel elines nes a SAB ABA A dose e of X or more e ea each week eek in indic icates poor

• or control
• l. What is

is X?

A. 1 B. 2 C. 3 D. 5 E. 10

A. Metabolic acidosis with respiratory compensation B. Respiratory acidosis C. Metabolic acidosis without respiratory compensation D. Metabolic alkalosis

• PaO2 – 14 (11-13 kPa)
• pH – 7.33 (7.35 – 7.45)
• PaCO2 – 3.0 (4.7 – 6.0 kPa)

In Interpret t this AB ABG

Wh Which l level d does t the tr trachea b bifurcate a at? t?

A. T2 B. T3 C. T4 D. T5 E. T6

A A small child en enter ers the e clini nic after er swallowing ng a piec ece e of Lego ego, it’s th thought to be trapped in of th the bronchus, which one is most likely?

A. Left bronchus B. Right bronchus

CPH CPH Ch Cheat at Sheet

St Studying ng geo eographic c and nd tem emporal variation n in n di diseas ases

• Geographic studies are needed when causal factor doesn’t vary much between individuals in one place. Geographic

variation in health/disease occurs at different levels, between,

• Countries
• Regions
• Borough
• Neighbourhoods
• Time trends in health/disease occur at different levels
• Long-term trends
• Short-term, especially seasonal (e.g. winter peak of mortality, especially from cardiovascular, respiratory

disease.)

Un Unders rsta tandin ing tim g time tre trends

Pattern of time trends can distinguish between

• Period effect, a recent cause or one related to a recent time period. A change in mortality in all

age groups at the same time point suggests a cause operating at that time.

• Cohort effect, an early life cause, close to time of birth. A change in all age groups related to

year at birth, suggests a cause operating from early life.

Pi Pitfalls alls of

• f study

dying time trends ds

Potential pitfalls in studying time trends is assuming the trends are real, there could have been,

• Changes in ASCERTAINMENT (e.g. willingness to seek medical care, ability to obtain it)
• Changes in DIAGNOSIS (e.g. changes in customs, diagnostic equipment)
• Changes in RECORDING of information
• Changes in POPULATION STRUCTURE (age, gender etc)
• In time trend studies, the analyses are based on population groups rather than individuals; exposure and outcome not

necessarily linked in individuals

• Possibility of confounding

Best way to overcome these problems is to complement these investigations with a study relating the potential disease cause (the `exposure’) to the disease outcome in individuals (case control studies, cohort studies, randomized trials)

Pi Pitfalls alls of

• f geog
• grap

aphic studi dies

• Differences in ascertainment between countries (e.g. willingness to seek medical care, ability to obtain it)

Solution: population-wide survey, objective measures

• Differences in diagnosis between countries (e.g. local customs, diagnostic equipment)

Solution: standardise diagnostic criteria, e.g. WHO, International Classification of Diseases

• Differences in recording of information

Solution: standardise diagnostic criteria, e.g. WHO, International Classification of Diseases

• Differences in population structure (age, gender etc)

Solution: take account of age and gender in comparisons of disease rates

Ma Main in t type pes o

• f g

f geographic phical s studie ies

Study Definition Pitfalls

Ecological study Used to understand geographical variation and study specific disease causes. the unit of observation is the population or community (rather than the individual).

• 1. Analyses based on population groups rather than individuals – the

assumptions that exposure and outcome are also related in individuals may not be true, ‘ecological fallacy’

• 2. Often groups differ from one another in many ways – always a

possibility of confounding (i.e. another factor in play related to both exposure and disease) Migration study Studying people migrating between geographic locations with different disease experiences. Can help to separate effects of:

• Adult environment
• Early environment and/or genetic factors
• Can study disease risk in

1st and 2nd generation immigrants

• 1. Selection bias – are the people who migrated the same as the people

who were left behind?

• 2. Information bias – do immigrants provide information consistent with

non-migrants in surveys?

• 3. Potential influence of stress of migration – could this contribute to

disease patterns observed?