Case 5 Flashcards
Compensating organ response to increased pCO2 as a result of hypoventilation in COPD
Kidney retains HCO3- (slow response - hours/days)
Compensating organ response to decreased pCO2 as a result of a panic attack (hyperventilation)
Kidneys decrease retention of HCO3- in the tubules.
Compensating organ response to decreased HCO3- and increased CO2 in metabolic acidosis (e.g. DKA)
Hyperventilation by lungs, to drive off CO2
Compensating organ response to metabolic acidosis due to severe vomiting
Hypoventilation to reduce loss of CO2
Inspiration
Contraction of diaphragm and external intercostal muscles. Increased volume of thorax Decreased intrapleural pressure Draws air into lungs Decreased pressure in alveoli Therefore, expansion of alveoli
Expiration
Relaxation of diaphragm and external intercostal muscles Decreased volume of thorax Increased intrapleural pressure Forces air out of lungs Increased pressure in alveoli Therefore, recoil of alveoli
Compliance
Ease at which the chest volume can be changed
Elastic recoil
Ability of the lungs to recover their original shape after stretching
What is the function of lung surfactant?
Since alveoli have a small radius and moist walls, surface tension can be generated causing walls to collapse.
Lung surfactant forms a fluid layer that lines the alveoli, decreasing surface tension and preventing collapse of alveoli. Therefore, increased compliance of lungs.
Lung surfactant is secreted by…
Type II epithelial cells
Factors which affect lung compliance
Elasticity of lung tissue (e.g. pulmonary fibrosis decreases compliance)
Obesity (reduces contraction of diaphragm)
Pulmonary blood flow
Bronchial smooth muscle tone
Changes in bone structure around lungs (e.g. rub fracture)
Maximum airway resistance in the respiratory tract
Segmental bronchi - airflow is high but cross sectional area is low
Factors affecting airway resistance
Radius of airway
Flow pattern - laminar or turbulent (mucus will cause turbulent flow)
Obstruction (e.g. tumor, inhaled particle)
Viscosity and density of gas mixture
FEV1
Volume of air forcefully exhaled in 1 second
FVC
Volume of air that can be maximally forcefully exhaled
Silicosis
Caused by inhalation of silicon dioxide.
Toxic to macrophages
Readily initiates fibrosis (may also have some streaks of calcification around hilar lymph nodes)
Asbestosis
Fibrosis caused by asbestos
Other symptoms: clubbing, inspiratory crackles
Mesothelioma of the lung
Commonly presents as pleural effusion with chest wall pain
Also caused by asbestos
Pneumoconiosis
Dust particles retained in small airways and alveoli. Common in coal workers. Has an immediate fibrogenic effect.
Pulmonary fibrosis on an X-ray
Reticular (net-like) shadowing of lung peripheries, typically more prominent towards lung bases.
Contours of the heart less distinct (‘shaggy’)
Later becomes more widespread, leading to lung volume loss.
Production of mucus in the lungs…
Goblet cells in epithelium of respiratory tract
Function of mucus in the lungs
Trap inhaled particles, preventing them from entering the lungs. Combination of mucus and inhaled particles can be swallowed.
Area of greatest ventilation in the lungs
Apex - since intrapleural pressure is greater here.
Area of greatest perfusion in the lungs
Base - since blood pressure is greatest here.
Bohr Shift
Increased unloading of oxygen in response to: Increased pCO2 Increased [H+] Increased temperature Increased 2-3 BPG
Occurs at metabolising cells to supply them with oxygen.
Oxygen dissociation curve shifted to the right.
Hypoventilation
Ventilation does not meet metabolic demand.
Occurs in diseases which increase physiological dead space and in paralysis of respiratory muscles
Hyperventilation
Ventilation in excess of metabolic needs OR CO2 exhaled at a greater rate than production.
Occurs during acute asthma attacks, under stress and at high altitude.
Functions of conducting portion of respiratory tract
Humidify - by serous and mucous secretions
Warmed - by underlying blood vessels
Filtered - i.e. particles become trapped in mucous to be swallowed
Structures which make up the conducting portion of respiratory tract
Nasal cavities Nasopharynx Larynx Trachea Bronchi Bronchioles
Function of respiratory portion of respiratory tract
Interface for passive exchange of gases between the atmosphere and blood
Structures which make up the respiratory portion of the respiratory tract
Respiratory bronchioles
Alveolar ducts
Alveolar sacs
Alveoli
Epithelium found in respiratory portion of tract
Ciliated cuboidal epithelium, containing some secretory cells called CLARA cells
Type I pneumocytes
Large flattened cells (thin barrier to gaseous exchange)
95% of total alveolar area
Connected to each other by tight junctions.
Involved in gaseous exchange
Type II pneumocytes
5% of total area
60% of total number of cells (very small)
Secrete lung surfactant to reduce surface tension
Connected to epithelium and other cells by tight junctions.
Foamy cytoplasm due to lamella bodies (GAGs, proteins, phospholipids)
Composition of lung surfactant
80% Phospholipids (inc DPCC)
10% Neutrolipids (mostly cholesterol)
10% Surfactant proteins
Left lung lies in close proximity to…
Heart
Arch of aorta
Thoracic aorta
Oesophagus
Right lung lies in close proximity to…
Heart
Oesophagus
IVC and SVC
Azygous vein
Lobes of the left lung…
Superior and inferior
Lobes of the right lung
Superior, middle and inferior
Outer surfaces of lungs:
Mediastinal (between the two lungs)
Cervical (upper, lateral)
Costal (lower, lateral) - smooth, convex and separated from ribs by costal pleura
Diaphragmatic
Blood supply to the lung parenchyma
Deoxygenated blood enters via 2 pulmonary arteries.
Oxygenated blood leaves via 4 pulmonary veins.
Blood supply to bronchi
Bronchial arteries arise from descending aorta .
Venous drainage via bronchial veins into azygous (right) and hemiazygous (left) veins
Sympathetic innervaton of lungs
Derived from sympathetic trunk.
Stimulates relaxation of bronchial smooth muscle and vasoconstriction of pulmonary vessels.
Parasympathetic innervation of lungs
Supplied by vagus nerve.
Stimulates secretion from bronchial glands, contraction of bronchial smooth muscle and vasodilation of pulmonary vessels.
Visceral afferents of lungs
Conduct pain impulses to sensory ganglion of vagus nerve.
What is a pulmonary embolism?
Obstruction of pulmonary artery by a substance travelled from elsewhere in the body.
Most commonly thrombus.
Can be fat (following bone fracture/orthopod surgery) or air (following cannulation in the neck).
Clinical features of Pulmonary Embolism
Dyspnoea
Chesty cough
Haemoptysis
Tachypnoea
Well’s Score
Calculates risk of DVT/PE
Treatment of Pulmonary Embolism
Anticoagulation and thrombolytic therapy (decrease size of embolism)
What are pleura?
Serous membrane enfolding both lungs. Reflected upon the walls of the thorax and diaphragm.
Visceral - covers lungs, extending into interlobular fissures.
Parietal - covers internal surface of thoracic cavity (mediastinal, cervical, costal and diaphragmatic)
Pleural Cavity
Space between parietal and visceral pleura.
Contains serous fluid which lubricates surfaces of pleurae and generates surface tension (so that when thorax expands, the lungs also expand).
Pleural recesses
Where opposing surfaces of parietal pleura meet.
Costomediastinal and costodiaphragmatic
Of clinical importance since they provide a location for fluid collection.
How does nervous supply differ between parietal and visceral pleura?
Parietal - innervated by phrenic and intercostal nerves. Sensitive to pain, temp and pressure. Produces a well localised pain.
Visceral - autonomic innervation from vagus nerve and sympathetic trunk only. Sensitive only to stretch.
Blood supply to parietal pleura
Intercostal arteries
Blood supply to visceral pleura
Internal thoracic arteries (bronchial circulation which also supplies lung parenchyma)
What is a Pneumothorax?
When air or gas is present within pleural space.
Can be spontaneous (w/ or w/o underlying respiratory disease) or traumatic
Clinical features of pneumothorax
Chest pain
Shortness of breath
Asymmetrical chest expansion
Hyperresonance on affected side due to excess air.
Normal response to allergens in the lungs
Driven by Th2 lymphocytes.
Facilitate IgE synthesis (via IL4) and eosinophilic inflammation (via IL-5)
Why can exercise cause coughing?
When out of breath, people often start to breath in through their mouth - breathing in cold, dry, unconditioned air. Results in bronchospasm.
Trachealis muscle
Smooth muscle that bridges the gap between the free ends of C-shaped cartilages at the posterior border of the trachea.
Contracts to constrict trachea, allowing air to be expelled with more force e.g. during coughing.
Structure of large central airways
Pseudostratified epithelium
Surrounded by mucous secreting and serous (water secreting) cells
Surrounded by C-shaped cartilagenous ring, joined at each end by trachealis muscle.
How does structure of tertiary bronchus differ from large central airways?
Contains columnar epithelium rather than pseudostratified.
Contains less cartilage and its cartilage is discontinuous.
More collapsible, easier to change diameter.
How does structure of bronchioles differ from tertiary bronchus?
No cartilage
More smooth muscle
Clara cells
Clara cells
Club cells/Bronchiolar exocrine cells
Dome shaped with short microvilli
Protect bronchiolar epithelium - secrete uteroglobulin and detoxify harmful substances (protect against oxidative pollution)
Also act as a stem cell, multiplying and differentiating into ciliated cells to regenerate bronchiolar epithelium.
Mucus secretion into the bronchioles
Vagal nerve ending releases ACh (parasypathetic)
ACh binds to M3 receptor on serous cells.
Cl- secreted into lumen of submucosal gland. Promotes secretion of fluid into lumen.
Effect of parasympathetic activation on the lungs
Fight and prevent infection
Bronchoconstriction
Vasodilation (ready to mobilise neutrophils during infection)
Mucus gland and goblet cell secretion
Effect of sympathetic activation on the lungs
Fight or flight response
Bronchodilation
Vasoconstriction
Modulate cholinergic transmission.
Cough Reflex
Defensive reflex within respiratory tract.
Forced expulsive manouvre usually against a closed epiglottis which aims to actively repel irritant or foreign body from lungs e.g. sputum
Expiratory reflex
Strong expiration without a preceding in-draw of breath.
Aims to prevent aspiration into lungs.
C fibres in the lungs
Arise from Jugular neurons
Thin, unmyelinated (slow, <2m/s)
Contain neuropeptides: Substance P, CGRP and neurokinin A
Also contain tachykinin.
How does activation of C-fibres generate a proinflammatory environment?
C fibres release substance P, CGRP and neurokinin A.
These neuropeptides act on neurokinin 1, 2 or 3
Activation of NK1 = mucus hypersecretion and airway smooth muscle contraction.
Activation of NK1 = extremely potent bronchoconstriction
Definition of chronic cough
Duration >8wks
Definition of acute cough
Sudden onset
Duration up to 3 weeks
Definition of sub-acute cough
3-8weeks duration
Emphysema
Abnormal and permanent dilatation of alveoli with destruction of walls
Pathophysiology of emphysema
Degradation of elastin due to:
Hyperinflation of alveoli
Destruction of alveolar and capillary walls
Therefore, loss of elastic recoil and collapse of small airways.
Chronic bronchitis
Inflammation of bronchi and bronchioles
Pathphysiology of chronic bronchitis
Hypertrophy of mucosal glands and increased number of goblet cells causing mucus hypersecretion.
Mucociliary escalator dysfunction - mucus is not removed from lumen causing an obstruction.
Thickening of bronchial wall due to inflammation also causes narrowing - therefore further obstruction.
Causes of COPD
Smoking (only occurs in 30% of smokers)
Genetic factors (alpha-trypsin deficiency causes emphysema)
Occupational (silica, coal dust)
Biomass fuel emission
Nutrition - diet low in antioxidant vitamins
Low birth weight
Maternal smoking
Clinical features on examination of a patient with COPD
Hyperinflated chest (air trapping) Breathing quickly Using accessory muscles of respiration Cachectic Reduced breathing sounds/wheezing
Symptoms of COPD
Progressive dyspnoea Reduced exercise tolerance Productive cough Wheeze Winter exacerbation Fatigue Weight loss/loss of appetite Oedema
Conditions associated with COPD
Osteoporosis (stimulation of osteoclasts by inflammatory cytokines) Type II diabetes Peptic ulcers CVD (25% chance) Renal Failure Lung cancer Reduced wound healing
CXR of COPD
Flattening of diaphragm (extreme case - floating heart sign)
Difficult to see ribs - osteopenic due to long term steroid use
Bullous Emphysema - upper zones contain areas of low density (black) with thinning of pulmonary vessels
May have consolidation due to infection.
FEV1/FVC ratio > 0.7
Normal or restrictive (if both values are low)
FEV1/FVC ratio < 0.7
Obstructive e.g. Emphysema
How does alpha 1 antitrypsin deficiency cause emphysema?
Alpha 1 antitrypsin inhibits elastase which breaks down elastin.
When A1A is deficient, elastase breaks down more elastin in the lungs causing loss of elasticity.
Physical mechanisms of lung defence
Humidification
Particle expulsion - cough or sneeze
Pathophysiology of bronchiectasis
External insult (infectious or toxic) causing bronchial wall inflammation or destruction.
Ciliary dyskinesia +/- altered bronchiodynamics (smooth muscle cannot expand/contract as easily.
Ineffective mucus clearance due to loss of cilia.
Bacteria in mucus are able to colonise airway - results in chronic or recurrent infection.
Cause of bronchiectasis
Any lung damage: Pneumonia Large PE Immune deficiency RA Inhalation of foreign body Alpha 1 antitrypsin deficiency Allergic Bronchopulmonary Aspergillosis Idiopathic (32%)
Symptoms of Bronchiectasis
Chest pain (31%) Breathlessnes (83%) Cough w/ daily sputum (75%) Haemoptysis (50%) - new fragile blood vessels generated to help damaged organ. Weight loss Malaise Low energy
Signs of bronchiectasis
Course crackles on early inspiration in lower lobes (50%)
Large airway rhonchi (44%) - low pitched, snore like sounds
Finger clubbing (rare)
Clinical features of bronchiectasis
Young age of onset of symptoms (have had symptoms for many years)
No history of smoking
Pseudomonas aeruginosa in sputum
Investigations used in diagnosis of bronchiectasis
CXR (abnormal in 90% of cases)
CT scan - shows signet rings due thickening of walls of bronchioles
Tests for CF, A1A deficiency and other assoc. conditions
Serum antibodies
FBC and CRP
CXR in Bronchiectasis
Coarsening of lung markings.
BUT may have a normal CXR, CT is needed to confirm diagnosis.
Indication for salbutamol
Acute exacerbation of COPD/Asthma
Route of administration of salbutamol
Asthma/COPD - inhalation
Status asthmaticus - IV or nebulised
ADRs of salbutamol
Hand tremor Headache Hypokalaemia Cardiac arrhythmia Uticaria (itchy rash)
Contraindications of salbutamol
Arrhythmia
CVD
Hypokalaemia
MOA of salbutamol
Short acting Beta 2 agonist causing bronchodilation (relaxation of smooth muscle)
MOA of ipratropium
Short acting inhibition of M1-3 muscarinic receptors causing bronchodilation through relaxation of smooth muscle
Indication for Ipratropium
Acute, rescue drug for exacerbations of asthma/COPD
ADRs of Ipratropium
Constipation Cough Dry mouth diarrhoea GI disturbance Headache
Contraindications of Ipratropium
Arrhythmia
Cardiac failure or MI in last 6 months
MOA of beclametasone
Steroid - forms a complex with corticosteroid receptor. Complex acts as a transcriptional regulator. Upregulates anti inflammatory proteins and down regulates pro inflammatory mediators.
Indication for beclametasone
Preventative anti inflammatory drug
Used in conjunction with preventers
ADRs of beclametasone
Long term immunosuppression
Cushing’s Syndrome
Osteoporosis
Oral Thrush
Potentially decreased growth velocity in children
Increased risk of pneumonia in COPD patients
Contraindications of beclametasone
Immunocompromised
Diabetic
Management of infective exacerbation of bronchiectasis
- Sputum culture and sensitivity testing
- Abx - 1st line: Amoxicillin. If contraindicated: Clarythromycin
- SABA - Salbutamol
- ICS if asthmatic or COPD
- Ensure suitable airway clearance technique taught by physio
General management of COPD
Smoking cessation
Annual flu vaccination
Pneumococcal Vaccination
First line: SABA or SAMA
Patient with COPD is receiving a SABA/SAMA which is not effectively managing their symptoms. What alternative treatment can be offered?
If FEV1 > 50%: LABA (salmeterol) or LAMA (tiotropium)
If FEV1 < 50%: LABA (salmeterol) + ICS (Fluticasone) OR LAMA (tiotropium)
Indication for theophylline in management of COPD
Only when all other treatment options have been tried
Indication for mucolytics (Mucodiene, Bromhexine) in management of COPD
Only for patients with chronic productive cough and only continued if symptoms improve with treatment.
Common causes of infectious exacerbations of COPD
Haemophilus influenza
Streptococcus Pneumoniae
Moraxella Catarrhalis
Management of infectious exacerbation of COPD
Increase frequency of bronchodilator (and consider giving via nebuliser rather than inhaler)
Prednisolone
NICE do not support treatment with oral antibiotics. Only given when sputum is purulent or there are clinical signs of pneumoniae.
What are the advantages of nebulised antibiotics over oral?
Targeted - therefore reduced systemic side effects (but increased local side effects) and smaller dose is required
What are the advantages of oral antibiotics over nebulised?
Cheap
Quicker and easier
Symptoms of pneumoniae
Dyspnoea Chest pain (pleuritic) Cough (with purulent sputum) Fever General malaise Confusion or delirium
MOA of salmeterol
Long acting inhaled B2 agonist (LABA)
ADRs of salmeterol
Angioedema Cardiac arrhythmias Hand tremors Uticaria (itchy rash) Hypokalaemia
Contraindications of Salmeterol
CVD
Arrhythmia
Hypokalaemia
MOA of Tiotropium
Long acting inhibition of muscarinic (M3) receptors (LAMA)
ADRs of Tiotropium
Constipation Diarrhoea Dry mouth GI disturbance Headache
Contraindications of Tiotropium
Arrhythmias
Cardiac failure or MI in the past 6 months
Components of respiratory epithelum
Pseudostratified ciliated columnar with goblet cells
Anatomical dead space V:Q ratio
Ventilated alveoli which are not perfused e.g. pulmonary embolism
Va:Q = infinite
Shunting V:Q ratio
Perfused tissue which is not ventilated
Va:Q = 0
Physiological shunting
Bronchial arteries which supply lung tissue
Pathophysiological shunting
Fluid filled alveoli
How does the body maintain V:Q ratio?
Modulation of blood flow - if pO2 decreases, vasoconstriction occurs. Therefore, redirecting blood flow away from poorly perfused areas.
This is the opposite to systemic circulation
Ideal V:Q
1
Change in breathing pattern as a result of damage to the pons
Ataxic breathing with irregular period apnoea - Pons is involved in fine tuning
Central chemoreceptors are located in…
Ventrolateral surface of the medulla
Central chemoreceptors detect…
Changes in pH of the surrounding CSF which is proportional to pCO2
Changes in pulmonary vascular resistance
PVR decreases as blood pressure increases as pulmonary capillaries which were closed at rest will open.
Ensures that there is sufficient time for gaseous exchange to occur.
Pulmonary wedge pressure
Indirect measurement of pressure of blood in left atrium
Why is intrapleural pressure higher in base of lungs than in the apex?
Lung base weighs more than the apex
Flow of blood in pulmonary capillaries 3cm above the heart
Pulsatory
Pressure in artery > Pressure in alveoli > Pressure in vein
Core pulmonale
Enlargement or failure of right ventricle caused by increased vascular resistance or high lung blood pressure.
Signs of cor pulmonale
Cyanosis Oedema Raised JVP Ascites SOB Prominent neck and facial veins
Type I Respiratory failure
Oxygenation failure
Hypoxia without hypercapnia
Due to V:Q mismatch, shunting or low altitude
Type II Respiratory failure
Ventilation failure
Hypoxia with hypercapnia
Due to COPD and pulmonary fibrosis
