8. Sensory Aspects of Respiratory Disease

Question 1

What is the difference between a symptom and a sign?

Answer 1

Symptom: an abnormal/worrying sensation that leads the person to seek medical attention (e.g. cough, chest pain, shortness of breath)

Sign: an observable feature upon physical examination of the patient (e.g. hyperinflation of the chest wall, dullness on percussion of chest wall, increased respiratory rate, reduced movement of chest wall)

Question 2

Outline the mechanism of symptom recognition

Answer 2

The mechanism of symptom recognition may be physiologic or pathological stimulus leading to conscious sensation

o Neurophysiology:

Sensory stimulus –> transducer –> excitation of sensory nerve –> integration within the CNS –> sensory impression

o Behavioural psychology:

Sensory impression –> perception –> evoked sensation

Question 3

Outline the prevalence of respiratory systems

Answer 3

Prevalence of respiratory symptoms:

o Cough - 3rd most common GP complaint; 10-38% of respiratory outpatients

o Chest pain - most common pain for seeking attention

o Shortness of breath (SOB/dyspnoea) - 6-27% of general population, 3% A&E visits

Question 4

Outline the epidemiology of coughs

Answer 4

Most prevalent is chronic coughs correlated to smoking, but also associated with current asthma and environmental tobacco smoke exposure

Prevalence from 7.2-18%, with a reduced prevalence involving sputum production

Question 5

Define sputum

Answer 5

A mixture of saliva and mucus coughed up from the respiratory tract, typically as a result of infection or other disease and often examined microscopically to aid medical diagnosis

Question 6

Define cough

Answer 6

A crucial defence mechanism protecting the lower respiratory tract from inhaled foreign material and excessive secretion, secondary to mucociliary clearance

It is important in lung disease when mucociliary clearance is impaired, and mucus production is increased

Question 7

Summarise the importance of coughs and how they work

Answer 7

The expulsive phase of a cough generates a high velocity of airflow, facilitated by bronchoconstriction and mucus secretion

Effectively, everyone has a cough; it is used to remove 30-100ml of fluid from the airways each day; this is to reduce risk of disease

Question 8

Outline the ‘cough receptor’

Answer 8

‘Cough receptor’ - nerve profile situated between a goblet cell and a columnar epithelial cell, which when stimulated leads to a cough:

o These are rapidly adapting irritant receptors which are located within airway epithelium, most numerous on the posterior wall of the trachea

o At the main carina (last cartilage before tracheal bifurcation) and large branching points, they are less numerous

o They are less numerous in the more distal airways, and are absent beyond respiratory bronchioles

o They are also in the pharynx; possibly also in the external auditory meatus, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium and stomach

o Stimuli: larangeal and tracheobronchial receptors response to chemical and mechanical stimuli

o Retinoic acid receptors (RARs) are considered to be cough receptors

Question 9

Outline the Retinoic Acid Receptor (RAR) and Retinoic Acid

Answer 9

The retinoic acid receptor (RAR) is a type of nuclear receptor which can also act as a transcription factor that is activated by both all-trans retinoic acid and 9-cis retinoic acid

They are considered to be cough receptors

Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A required for growth and development

Question 10

Outline ‘sensory receptors’ related to coughs

Answer 10

Sensory receptors are also present in the lungs and airways, including slowly adapting stretch receptors, rapidly adapting stretch receptors and C-fibre receptors:

o Slowly adapting stretch receptors – located in the airway smooth muscle, are myelinated nerve fibres predominantly in trachea and main bronchi; they are mechanoreceptors which respond to lung inflation

o Rapidly adapting stretch receptors – located in the naso-pharynx, larynx, trachea, bronchi; they are small, myelinated nerve fibres which respond to both mechanical/chemical irritant stimuli and inflammatory mediators

o C-fibre receptors – are ‘free’ nerve endings found in the larynx, trachea, bronchi and lungs; they are small unmyelinated fibres which respond to chemical irritants and inflammatory mediators by releasing neuropeptide inflammatory mediators: substance P, neurokinin A, calcitonin gene related peptide

Stimuli include mechanical irritants (dust, mucous, food, drink) or chemical (noxious, intrinsic inflammatory agents)

Question 11

Outline neurokinin A

Answer 11

Neurokinin A, formerly known as Substance K, is a neurologically active peptide translated from the pre-protachykinin gene

Neurokinin A has many excitatory effects on mammalian nervous systems and is also influential on the mammalian inflammatory and pain response

Question 12

Outline calcitonin

Answer 12

Calcitonin is a hormone that is produced in humans by the parafollicular cells (commonly known as C-cells) of the thyroid gland

Calcitonin is involved in helping to regulate levels of calcium and phosphate in the blood, opposing the action of parathyroid hormone by reducing blood Ca2+ levels

Question 13

Outline the nervous pathways related to coughs

Answer 13

Afferent pathways for the stimuli from lungs via Vagus nerve (X), and from throat via superior laryngeal nerve; both stimulate the ‘cough centre’ in the medulla –> pathway to cerebral cortex

Central pathways; the cough centre in the brain stem is probably diffusely located

Vagal afferents relay impulses to an area near the nucleus tractus solitarius, then is integrated in a ‘cough centre’ in the medulla oblongata:

o This is distinct from the respiratory centre -bulbopontine controller

Possible neurotransmitters involved: 5-hydroxytryptamine, gamma-amino-butyric acid (GABA):

o Opiates work centrally in suppressing cough, acting on the cough centre in the medulla

Efferent pathways; cerebral cortex –> cough centre –> glottis, diaphragm and expiratory muscles, i.e. motor neurones to respiratory muscles

Question 14

Contrast afferent and efferent neurons

Answer 14

Afferent neurons are sensory neurons that carry nerve impulses from sensory stimuli towards the central nervous system and brain, while efferent neurons are motor neurons that carry neural impulses away from the central nervous system and towards muscles to cause movement

Question 15

Outline the mechanics of coughing

Answer 15

Inspiratory phase: negative airflow occurs

Glottic closure: subglottic pressure increases, while the
glottis is closed

Expiratory phase (explosive): airflow increases rapidly, leading to sound

Question 16

Define glottis

Answer 16

The part of the larynx consisting of the vocal cords and the slit-like opening between them

It affects voice modulation through expansion or contraction

Question 17

Define epiglottis

Answer 17

The epiglottis is a flap in the throat that keeps food from entering the windpipe and into the lungs

Made of elastic cartilage covered with a mucous membrane, the epiglottis is attached to the entrance of the larynx

Question 18

Sketch a graph of the sound changes throughout a cough

Answer 18

[ See http://www.icsmsu.com/exec/wp-content/uploads/2011/12/ABS-Respiratory_System.pdf Page 57]

Question 19

Outline the causes of coughing

Answer 19

Acute infections - tracheobronchitis, bronchopneumonia, viral pneumonia, acute-on-chronic bronchitis, bordetella pertussis

Chronic infections - bronchiectasis, tuberculosis, cystic fibrosis

Airway diseases - asthma, chronic bronchitis, chronic post-nasal drip

Parenchymal diseases - interstitial fibrosis, emphysema

Tumours - bronchogenic carcinoma, alveolar cell carcinoma, benign airway tumours

Foreign bodies

Cardiovascular - left ventricular failure, pulmonary infarction, aortic aneurysm

Other diseases - reflux oesophagitis, recurrent aspiration

Drugs - angiotensin converting enzyme

Question 20

Outline the 2 main types of cough

Answer 20

Acute - < 3 weeks, most commonly due to the common cold (involves cough, post-nasal drip, throat clearing, nasal blockage and nasal discharge)

Chronic persistent - > 3 weeks on presentation to a respiratory clinic:

o Asthma and eosinophil associated

o Gastro-oesophageal associated

o Rhinosinusitis (post-nasal drip)

o Chronic bronchitis (‘smokers cough’)

o Bronchiectasis, Drugs, Post-viral, Idiopathic and other causes

Question 21

Outline the ‘common cold’

Answer 21

The common cold is a viral infectious disease of the upper respiratory tract that primarily affects the nose

The throat, sinuses, and larynx may also be affected

Signs and symptoms may appear less than two days after exposure to the virus

These may include coughing, sore throat, runny nose, sneezing, headache, and fever

People usually recover in seven to ten days, but some symptoms may last up to three weeks

Occasionally those with other health problems may develop pneumonia

Well over 200 virus strains are implicated in causing the common cold, with rhinoviruses being the most common

Question 22

Outline the 3 mechanisms of the gastro-oesophageal reflux of gastric contents

Answer 22

Occurs at pH ~2/3

1. Oesophageal bronchial reflex: activation of cough receptors occurs due to interconnecting neurones between the trachea and oesophagus
2. Direct action of protons on cough receptors: protons travel to the pharynx and stimulate cough receptors
3. Activation of brainstem cough centres

Question 23

Outline ‘activation of brainstem cough centres’ as a mechanism of the gastro-oesophageal reflux of gastric contents

Answer 23

3rd mechanism = neural mechanism

Plasticity of neural mechanisms: The nervous system is plastic, i.e. its sensitivity can be increased by chemical mediators

Chemical mediators (e.g. prostaglandin E2) increase the excitability of afferent nerves

The number of receptors and voltage-gated channels increases, e.g. TRPV-1 (transient receptor potential
vanniloid-1: calcium-permeable, non-selective cation channel)

Neurotransmitter levels increase (e.g. neurokinins in brain stem)

Question 24

Outline prostaglandin E2

Answer 24

Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin which is used as a medication

It is a direct vasodilator, relaxing smooth muscles, and it inhibits the release of noradrenaline from sympathetic nerve terminals

It does not inhibit platelet aggregation, where PGI2 does

Question 25

Outline PGI2

Answer 25

Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator

Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation

It is also an effective vasodilator

Prostacyclin’s interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage

It is used to treat pulmonary artery hypertension

Question 26

Outline the indications and triggers of chronic cough

Answer 26

Chronic cough indicates that patients have an increased cough reflex

Indications of chronic cough include:

o Irritation in the throat or upper chest

o Cough paroxysms are difficult to control

Triggers of chronic cough include:

o Deep inhalation

o Laughing

o Talking too much

o Vigorous exercise

o Smells

o Cigarette smoke

o Eating crumbles

o Cold air

o Lying flat

Question 27

Define paroxysm

Answer 27

A sudden recurrence or attack of a disease

Question 28

Outline the complications associated with coughing

Answer 28

Pneumothorax with subcutaneous emphysema

Loss of conciousness (cough syncope)

Cardiac dysrhythmias

Headaches

Intercostal muscle pain

Rupture of the rectus abdominis muscle

Social embarrassment

Depression

Urinary incontinence

Wound dehiscence (rupturing along a surgical incision)

Question 29

Outline treatment for coughs

Answer 29

Inhaled corticosteroids and inhaled beta-adrenergic agonists - for asthma, cough-variant asthma and eosinophilic bronchitis

Topical steroids, topical vasoconstrictors - for rhinosinusitis (post-nasal drip)

Proton-pump inhibitors, medical therapies - for gastro-oesophageal reflux

Stop ACE inhibitors - for ACE inhibitor cough

Antitussives:

o Opiates - codeine, pholcodeine, dextromethorphan

o Demulcents

o Aromatics

Question 30

Outline pneumothorax

Answer 30

A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall

Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath

A primary pneumothorax is one that occurs without an apparent cause and in the absence of significant lung disease, while a secondary pneumothorax occurs in the presence of existing lung disease

It is often called a collapsed lung, although that term may also refer to atelectasis

Question 31

Outline atelectasis

Answer 31

Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange

It may affect part or all of a lung

It is usually unilateral

It is a condition where the alveoli are deflated down to little or no volume, as distinct from pulmonary consolidation, in which they are filled with liquid

It is often called a collapsed lung, although that term may also refer to pneumothorax

Question 32

Outline ACE inhibitors

Answer 32

An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure

ACE inhibitors block the conversion of Angiotensin I (Ang I) to Angiotensin II (Ang II); they thereby lower arteriolar resistance and increase venous capacity; decrease cardiac output, cardiac index, stroke work, and volume; lower resistance in blood vessels in the kidneys; and lead to increased natriuresis (excretion of sodium in the urine)

Question 33

Outline proton pump inhibitors

Answer 33

Proton-pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of stomach acid production

Omeprazole was the first PPI to be sold

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells

The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion

Question 34

Outline the main targets for cough treatment

Answer 34

Acid pH inhibitors e.g. PPIs - airway epithelium and periciliary fluid

Opioids - CNS and vagus nerve

Bronchodilator: beta2-agonists and anticholinergics - airway smooth muscle

Anti-inflammatories: corticosteroids, leukotriene antagonists and Cox inhibitors - blood vessel-eosinophil
communication

Question 35

Outline the sensory input for chest pain

Answer 35

Nose: trigeminal nerve (V)

Pharynx: glossopharyngeal nerve (IX) and vagus nerve (X)

Larynx: vagus nerve (X)

Lungs: vagus nerve (X)

Chest wall: spinal nerves

Question 36

Name the 3 nervous pathways for chest pain

Answer 36

The pain pathway

The touch pathway

The conscious sensation of pain

Question 37

Outline ‘the pain pathway’ in relation to chest pain

Answer 37

Pain receptors: Aδ and C-fibres

Nerve fibres cross at the spinal level and synapse in
the thalamus

Nerves travel to the primary somatosensory cortex

Question 38

Outline ‘the touch pathway’ in relation to chest pain

Answer 38

Touch receptors: Aα and Aβ

Nerve fibres cross at the medullary level and synapse
in the thalamus

Nerves travel to the primary somatosensory cortex

Question 39

Outline ‘the conscious sensation of pain’ in relation to chest pain

Answer 39

Neurophysiology: sensory stimulus –> transducer –> excitation of the sensory nerve –> integration within the CNS –> sensory impression

Behavioural psychology: sensory impression –> perception –> evoked sensation

Question 40

Outline the thalamus

Answer 40

The thalamus is a small structure within the brain located just above the brain stem between the cerebral cortex and the midbrain and has extensive nerve connections to both

The main function of the thalamus is to relay motor and sensory signals to the cerebral cortex

Question 41

Discuss types of pain

Answer 41

Visceral and somatic

Visceral mechanisms are less well understood; vagueness also causes overlap of location

Difficulty in diagnosis of visceral pain level

Chronic pain is more complicated than acute pain and depends upon poorly defined neural mechanisms within the brain

Question 42

Define visceral pain

Answer 42

Visceral pain is pain that results from the activation of nociceptors of the thoracic, pelvic, or abdominal viscera (organs)

Visceral structures are highly sensitive to distension (stretch), ischemia and inflammation, but relatively insensitive to other stimuli that normally evoke pain such as cutting or burning

Question 43

Define somatic pain

Answer 43

Somatic pain is a type of nociceptive pain that is also referred to as skin pain, tissue pain, or muscle pain

Unlike visceral pain (another type of nociceptive pain that arises from internal organs), the nerves that detect somatic pain are located in the skin and deep tissues

Question 44

Summarise nociceptors

Answer 44

A nociceptor is a sensory neuron that responds to damaging or potentially damaging stimuli by sending ‘possible threat’ signals to the spinal cord and the brain

Question 45

Outline chest pain in both respiratory disorders and in non-respiratory disorders

Answer 45

Chest pain in respiratory disorders:

oChest wall - muscular or rib fracture

o Pleural pain

o Deep-seated, poorly-localised pain

o Nerve-root pain/intercostal nerve pain

o Referred pain: shoulder-tip pain of diaphragmatic irritation

Chest pain in non-respiratory disorders:

o CVD - myocardial ischaemia/infarction, pericarditis, dissecting aneurysm

o Gastrointestinal disorders - oesophageal rupture, gastro-oesophageal reflux

o Psychiatric disorders – panic

Question 46

Outline brain imaging during pain

Answer 46

Can be seen by positron emission tomography (PET) scans; the location of electrical activation is related to graded pain intensity

1. Somatosensory processing: primary and secondary somatosensory cortex, posterior insular cortex
2. Motor processing: cerebellum, putamen, ventral premotor cortex
3. Affective processing: anterior cingulate cortex, insular cortex
4. Attentional processing: anterior cingulate cortex, primary somatosensory cortex, ventral premotor
   cortex
5. Autonomic function: anterior cingulate cortex, anterior insular cortex

Question 47

Outline treatment for chest pain

Answer 47

Treat the cause, not just the symptoms

Chronic pain is more difficult to manage, although analgesics may reduce symptoms

Pair can be severe and refractory, in which case it is best dealt with at ‘pain clinics’

Question 48

Outline dyspnoea

Answer 48

‘Shortness of breath’

Symptom reported by the patient - occurs at inappropriately low levels of exertion and limits exercise tolerance

Unpleasant and frightening experience

Can be associated with feelings of impending suffocation

Poor perception of respiratory symptoms and dyspnoea may be life-threatening

Question 49

How is dyspnoea assessed, in terms of scales?

Answer 49

Via the use of the Modified Borg Scale, where:

0 = Nothing at all
0.5 = Just noticeable
1 = Very slight
2 = Slight
3 = Moderate
4 = Somewhat severe
5 = Severe
6
7 = Very severe
8
9 = Very, very severe
10 = Maximal

The clinical dyspnoea scale (of the American Thoracic Society) can also be used, where:

0 = None; not troubled by breathlessness except during strenuous exercise

1 = Slight; troubled by shortness of breath when hurrying on the level or walking up a slight hill

2 = Moderate; walks slower than people of the same age on the level because of breathlessness, or has to stop for breath when walking at their own pace on the level

3 = Severe; stops for a breath after walking ~100 yards (~91m) or after a few minutes on the level

4 = Very severe; too breathless to leave the house or breathless when dressing/undressing

Question 50

How is dyspnoea assessed, in terms of respiratory descriptors

Answer 50

Respiratory descriptors are used in conjunction with scales when assessing shortness of breath

Air-hunger cluster:

• Hunger for more air
• Urge to breathe more
• Starved for air
• Suffocation/smothering
• Short of breath
• Breaths feel too small

Work/effort cluster:

• Breathing requires effort
• Breathing requires work
• Breathing is uncomfortable
• Feels like heavy exercise
• Size of breaths feel too large

Tightness cluster:

• Tightness/constriction in the chest
• Heaviness in the chest

Question 51

Summarise the ways of assessing shortness of breath (SOB)

Answer 51

Volunteered comments & a clinicians’ assessment

Subjective rating scales:

o Visual analogue

o Modified Borg

Questionnaires:

o Exercise tolerance related - e.g. Baseline Dyspnea Index, Shortness of Breath Questionnaire

o Quality of life - e.g. SF36, St George’s Respiratory Questionnaire

Exercise testing:

o 6 minute walk test

o Shuttle test

Question 52

What is a visual analogue scale?

Answer 52

The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires

It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured

When responding to a VAS item, respondents specify their level of agreement to a statement by indicating a position along a continuous line between two end-po

Question 53

Outline some disorders which present with chronic dyspnoea

Answer 53

Impaired pulmonary function:

o Airflow obstruction (e.g. Asthma, COPD, tracheal stenosis)
o Restriction of lung mechanics (e.g. idiopathic pulmonary fibrosis)
o Extrathoracic pulmonary restriction (e.g. Kyphoscoliosis, pleural effusion)
o Neuromuscular weakness (e.g. Phrenic nerve paralysis)
o Gas exchange abnormalities (e.g. Right to left shunts)

Impaired cardiovascular function:

o Myocardial disease leading to heart failure
o Valvular disease
o Pericardial disease
o Pulmonary vascular disease
o Congenital vascular disease

Altered central ventilatory drive or perception:

o Systemic or metabolic disease
o Metabolic acidosis
o Anaemia

Physiologic processes (e.g. deconditioning, hypoxic high altitude, pregnancy, severe exercise)

Idiopathic hyperventilation

Question 54

Outline the general treatment of dyspnoea

Answer 54

Treat the cause (e.g. lung/cardiac)

Treatment of dyspnoea itself is difficult

Therapeutic options include:

o Add bronchodilators (e.g. anticholinergics or β-adrenergic agonists)

o Drugs affecting brain (e.g. morphine, diazepam)

o Lung resection (e.g. lung volume reduction surgery)

o Pulmonary rehabilitation (improve general fitness, general health, psychological well-being)

Question 55

Outline β-adrenergic agonists

Answer 55

Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, which widen the airways and result in easier breathing

They are a class of sympathomimetic agents which act upon the beta adrenoceptors

Beta adrenoreceptor agonist ligands mimic the action of adrenaline and noradrenaline signaling in the heart, lungs, and smooth muscle tissue, with adrenaline expressing the highest affinity

The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase; this, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP), cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue

Question 56

Outline anticholinergics

Answer 56

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system

These agents inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells

These drugs can be used to treat a variety of conditions, including respiratory disorders