Retired__LSS1__Respiratory Flashcards
1
Q
Recall the function of the respiratory mucosa, and the three main components
A
Function: line airways to protect from pathogens
Cells:- Ciliated: many mito for ATP to beat
- Goblet: mucin granules for secretion
- Submucosal: collecting ducts drain mucous
2
Q
Describe the structure of submucosal glands
A
Distal serous acini secrete antibacterials to the collecting duct, and proximal mucous acini secrete mucous; watery serous acini secretions wash mucous to duct
3
Q
Describe the structure and movement of cilia
A
Structure: actin polymers in 9+2 arrangement (9 pairs on outside and one in centre); dynein arms and ATPase allow columns to slide and bend cilia
Movement: beat in a synchronised (metachronal) rhythm to move leading edge of mucous
4
Q
Describe the function of the muco-ciliary escalator
A
Cilia beating moves mucous containing irritants and microbes upwards to larger airways for clearance by coughing or ingestion - only about 10ml in healthy people
5
Q
Recall the normal functions and proportion of alveolar macrophages and neutrophils
A
Macrophage Function: infiltrate alveoli and phagocytose inhaled microbes/toxin
Neutrophil Function: produce inflammatory mediators and serine/metallo proteinases
Proportions: 70% mac:30% neut
6
Q
Recall the effect of smoking on alveolar macrophages and neutrophils
A
Proportions: normally 70% mac:30% neut; in smoking changes to 30% mac:70% neut
Action: neutrophils secrete proteinases, oxidants and mediators to attract more inflammatory cells
7
Q
Define xenobiotic metabolism
A
Metabolism of foreign compounds deposited by inhalation, performed by phase I and II enzymes secreted by TII cells and macrophages
8
Q
Describe the innervation of the airways for sensory, constricting and relaxing functions
A
Sensory: Vagus afferents that travel to the CNS via nodose ganglion (or to spinal cord using dorsal root ganglion)
Constriction: parasympathetic Vagus cholinergic efferents cause constriction of airway smooth muscle cells
Relaxation: not sympathetic; nitric oxide producing pathways are activated that dilate airways
9
Q
Describe the cholinergic mechanism in response to airway irritants
A
1) Irritants activate sensory nerves (via Vagus and nodose ganglion to CNS)2) Central cholinergic reflex down Vagus PSNS nerve to PSNS ganglion3) Postganglionic neurones lead to muscarinic receptors that: a) Cause vasodilation b) Cause airway constriction c) Cause submucosal glands to secrete mucous
10
Q
State two forms of humoral control of the airways
A
Adrenaline: produced by adrenal gland; causes airway relaxation
Nitric Oxide: present in excess in epithelium to cause airway dilation
11
Q
Describe the effect of smoking on goblet, ciliated and epithelial cells
A
Goblet cells: number at least doubles (hyperplasia), with increased volume and viscosity of secretions to trap cigarette particles - inadvertently trapping microbes and leading to infection
Ciliated cells: severely depleted and beat asynchronously, and begin to appear in bronchioles and smaller airways - can no longer clear thicker mucous so reduced clearance leads to obstruction and infection
Epithelial cells: fibrosis occurs and alveolar walls are destroyed, leading to airway collapse and stenosis that prevents distal gas exchange
12
Q
Describe the pathophysiology of asthma
A
Airway epithelia become fragile, exposing sensory nerves, leading to increased airway responsiveness to stimuli; causes stimulation of sensory nerves that activate a cholinergic reflex; reflex causes bronchoconstriction and mucous secretion, with an influx of inflammatory cells producing mediators
13
Q
Describe airway remodelling seen in asthma
A
Hypertrophy of submucosal glands, airway smooth muscle and goblet cells occurs, leading to mucous plugs forming and remodelling of the airways
14
Q
Contrast involuntary and voluntary control of breathing
A
Involuntary (metabolic) control of breathing: occurs in the brainstem, and adjusts ventilation rate in response to pH levels in the blood
Voluntary (behavioural) control of breathing: occurs in the motor cortex, and controls breath holding, singing, talking etc - can be overridden by involuntary
15
Q
State the two regions of the brain in the metabolic centre (control of breathing), and the name/functions of the respiratory groups in each
A
Medulla: ventral (expiration), dorsal (inspiration)
Pons: apneustic (stimulates long, deep breathing and increases VT), pneumotaxic (inhibits apneustic to lower VT and inhibits phrenix nerve to stop inspiration)
16
Q
State the regions of the brain involved in behavioural control of breathing and the nerves involved
A
Motor cortex
Hypothalamus: can increase rate for fight/flightNerves:
- Phrenic (ANS): Diaphragm
- Vagus (ANS): Diaphragm, Larynx, Pharynx
- Posterio Thoracic (Somatic): intercostals
17
Q
Describe the location and stimuli detected by each type of chemoreceptor that influence breathing
A
Central: ventrolateral surface of medulla; detect pH of cerebrospinal fluid
Aortic: aortic arch; detect oxygen and CO2
Carotid: carotid sinus; detect oxygen, pH and CO2
18
Q
Describe the negative feedback of chemoreceptors
A
Alkalosis will result from a decreased level of CO2, suggesting hyperventilation, causing the chemoreceptors to signal the medulla to decrease ventilation rateConversely, acidosis will result from increased CO2, increasing the rate of firing to increase ventilation rate
19
Q
Compare the response speed of central and peripheral chemoreceptors
A
Central: perfusion of ECF bathing medulla slow, so central response slower
Peripheral: carotid bodies are hyperperfused, so can rapidly effect a change
20
Q
Describe the effect acidosis and hypoxia on responses to CO2levels
A
Acidosis: potentiates CO2responses
Hypoxia: low PO2increases sensitivity to carotid bodies to PCO2to increase breathing and correct hypoxia
21
Q
Describe the Hering-Bauer Reflex
A
Mechanoreceptors present in the bronchi and pleura detect stretch, so that upon maximal lung expansion these signal to the medulla/pons via the Vagus nerve to prevent overinflation; pneumotaxic centre of the pons inhibits apneustic centre to stop inspiration
22
Q
State which brain region and pathway controls breathing during sleep, including the respiratory neurones and their location
A
Brain Region: PreBotzinger Complex in the brainstem (rostroventrolateral surace of medulla - detect CSF pH)
Pathway: bulbospinal
23
Q
Describe the blood gas and ventilation changes during sleep
A
Ventilation: minute ventilation decreases to cause hypoventilation (same rate, decreased VT)
Blood Gases:- PaO2: decreases
- SaO2: barely changes as on flat part of ODC
- PaCO2: increases by 0.5kPa
24
Q
Explain the apnoeic threshold and how this may lead to central sleep apnoea
A
Hypercapnia: mandatory for sleep breathing
Apnoeic sleep threshold: PaCO2level needed for breathing to occur during sleep - if tidal volume does not decrease, then PaCO2 will not increase and will not breathe
Central sleep apnoea: Failure of tidal volume to decrease due to stroke or central congenital hypoventilation syndrome that means PaCO2 does not increase, and no effort is made to breathe
25
Describe the influences of sleep on the upper airway and skeletal muscles
Upper airway muscle: loses tone and becomes floppy - held open while awake - only diaphragm and eye muscles not paralysed during sleep
26
Explain obstructive sleep apnoea and the cycle produced
Obstructive sleep apnoea: if negative pressure generated during inhalation acts on floppy airways, can force shut rather than allow air to enter - exacerbated by excess adipose tissue applying external positive pressure that increases the problem
Sleep cycle: apnoea leads to arousal and patent airway, increasing ventilation that causes sleep to restart, but decreased accessory muscle function leads to hypercapnia and return of apnoea, again woken by effort of breathing against closed airway - stops deep sleep and can be debilitating
27
Explain how cardiorespiratory disease may be exacerbated by changes in breathing control during sleep
Pulmonary oedema: (fluid in the lungs) irritates receptors that causes hyperventilation, lowering PaCO2, hence causing cessation of breathing due to central sleep apnoea; affects 50% of heart failure patients and accelerates mortality (fluid results from pulmonary hypertension 2/2 heart failure)
28
Define compliance and elastance and explain the relationship between them
Compliance: tendency to distort under pressure (change in volume/pressure)
Elastance: inverse of compliance - tendency to resist change and recoil to original volume (change in pressure/volume)
29
Explain the composition and role of surfactant in ventilation and lung structure, including where it is secreted from
Surfactant: secreted by TII pneumocytes (80% polar phospholipids, 10% protein and 10% non-polar lipids)
Role: prevent collapse of small airways and alveoli, increasing compliance to reduce the work of breathing
30
Recall how resistance changes along airway generations
Increases as airways narrow, peaking at generation 4 then decreases
31
Recall the effect of changing lung volume on conductance and resistance
Conductance: linear increase with lung volume
Resistance: exponential decrease with increased lung volume
32
Describe the pressures and flow of air pre-, mid- and end-inspiration and during hard expiration
Pre-inspiration: at FRC, pressure in lungs and atmosphere is 0 so no-airflow; intrapleural space at -5 due to recoil
Mid-inspiration: intrapleural tension increased to -8 cmH2O, creating pressure gradient for air to move in
End-inspiration: intrapleural tension still at -8, but lung pressure and atmospheric are at 0 cmH2O
Hard expiration: creates bigger positive pressure in intra-pleural space; transmural pressure now surpassed collapsing pressure and airway should collapse - cannot maintain pressure and cartilage splinting prevents airway collapse
33
Explain the chest wall relationship and changes needed for inspiration/expiration
Chest wall relationship: chest wall has tendency to spring outwards while lung recoils inwards; forces are in equilibrium at end-tidal respiration (neutral position of intact chest)
Inspiratory muscle effort + chest recoil > lung recoil results in inspiration
Expiratory muscle effort + lung recoil > chest recoil results in expiration
34
Describe the arrangement of the pleural membranes
Lungs surrounded by visceral pleura, and chest wall covered in parietal pleura, with pleural cavity and fluid between the two (fixed volume) - double folded layer to allow two surfaces to work together
35
Describe the mechanics of ventilation
Diaphragm contracts to flatten, while ribs move upwards and outwards to increase lung volume and decrease Palv so that Palv < Patm and causing inspiration; recoil causes Palv > Patm so air is expelled
36
Describe the three compartment model and the pressures at rest
"Palv: alveolar pressure; 0 cmH2O at rest
Patm: atmospheric pressure; 0 cmH2O at rest
Ppl: pleural pressure; -5 cmH2O at rest"
37
Describe PTT, PTP, and PRS including the normal pressures
PTT: transthoracic (intraplueral - atmospheric); -5 cmH2O
PTP: transpulmonary (intraalveolar - intrapleural); 5 cmH2O
PRS: respiratory system (intraalveolar - atmospheric); 0 cmH2O
38
Descibe the normal pressure-volume relationship of the lungs
"Sigmoid shaped graph where at no external pressure (from the intercostals and diaphragm), a small change in pressure results in a large change in volume, and at extremes a large change in pressure is required to effect a change in volume (uncomfortable)
"
39
Describe the changes in pleural pressure in forced inhalation and exhalation
Forced inhalation: outward muscle force is larger than the inward recoil force, leading to the pulling apart of the pleura, increasing the negative pressure to -8 cmH2O
Forced exhalation: inward muscle force is larger than the outward recoil force, leading to an increase in pleural pressure to -2 cmH2O
40
Describe the changes in the pressure-volume graph seen in restrictive and obstructive lung disease
"
Restrictive: squashed reduced vital capacity; stretched because more effort to move air in so stretched - chest wall:lung interface less compliant
Obstructive: operates at higher volumes with larger vital capacity as tissue is more compliant
"
41
Differentiate between tidal and maximal ventilation
Tidal Breathing: 75% due to diaphragm contraction and 25% external intercostals with passive recoil
Maximal ventilation: Use of accessory muscles and internal intercostals to effect a much larger change in volume and hence gas exchange
42
Differentiate between ventilating fluid and air filled lungs
Fluid-filled lungs: water-water interface increases compliance, so fluid filled lungs expand under greater pressure
Air-filled lungs: lack of water-water interface decreases compliance, so a much larger change in pressure is needed to inflate the lungs
43
Contrast signs and symptoms
Symptoms: abnormal or worrying sensation that leads person to seek medical attention e.g. Cough/chest pain/SOB Signs: observable features on physical examination e.g. Hyperinflation, dullness on percussion, increased resp rate
44
State the name, location, myelination and stimuli of sensory respiratory receptors
- Slowly Adapting Stretch Receptors: myelinated mechanoreceptors in the trachea and bronchi sensitive to lung inflation
- Fast Adapting Stretch Receptors: small, myelinated fibres in the naso-pharynx, pharynx, trachea and bronchi sensitive to chemical/inflammatory stimuli
- C Fibres: unmyelinated fibres with free nerve endings in the larynx, trachea and bronchi that detect capsaicin and irritants, releasing neuropeptide inflammatory mediators
45
Describe the afferent neural pathways, efferent neural pathways and muscles involved in a cough
Afferent neural pathways: stimulation of irritant receptors leads to firing down Vagus nerve to cough centre in medulla
Efferent neural pathways: activate motor pathways to effect changes in breathing and cause expiratory airflow
Muscles involved: glottic muscles and expiratory muscles
46
Summarise the schema and function of a cough
Schema: Irritant receptors stimulated, afferent pathway via Vagus nerve to cough centre in medulla, motor pathway causes stimulation of glottic and expiratory muscles
Function: defence mechanism to protect LRtract from inhaled foreign material and excess mucous secretion, secondary to mucociliary clearance
47
Explain the mechanism of a cough
1) Inspiratory phase with negative flow during inhalation 2) Glottic pressure in the minimum flow phase (glottis closes to generate pressure) 3) Glottis opening 4) Expiratory phase
Trachea: intrathoracic pressure increases causing invagination of the trachea to form a crest shape and increase flow
48
Recall common causes of a cough and differentiate between acute and chronic coughs
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Common causes of cough: acute/chronic infection, airway disease, parenchymal disease, tumours, aspirated foreign bodies, middle ear pathology, CVD and drugs
Acute cough (<3 weeks): caused by common cold, linked to post nasal drip, throat clearing, nasal blockage and nasal discharge
Chronic cough (>3 weeks): may be asthma, GO reflux, postnasal drip, chronic bronchitis, bronchiectasis, ACE inhibitors or post-viral
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49
Summarise treatment strategies for general and disease-specific coughs, naming possible drugs
Symptomatic Suppressants:
- Central: opiates (codeine/dextromorphan)
- Peripheral: moguistine/levodropropizine
Disease-Specific:
- Eosiophil: corticosteroids
- Post-Nasal drip: steroids
- GORD: proton pump inhibitors
50
Compare somatic and visceral pain
Somatic pain: well localised and specific due to the highly specific innervation of muscles and dermatomes
Visceral pain: not the same as somatic pain and is difficult to localise/diffuse in character because the number of visceral afferents is less than the number of somatic afferents - thoracic visceral pain often presents similarly with overlapping patterns of referral, localisation and quality
51
Describe the afferent neural pathways and brain regions involved in nociception
Afferent neural pathways: pain uses the spino-thalamic tract, with a-delta/C-fibres entering the dorsal horn, immediately crossing and then passing up the tract to the thalamus and then to the primary somatosensory cortex
Brain regions involved: somatosensory processing occurs in the primary somatosensory cortex (motor in the cerebellum, attentional in primary somatosensory and autonomic in the cingulate/insular cortexes)
52
Explain the concept of referred pain, and typical presentations of cardiac/MSK problems and diaphragmatic irritation
Referred pain: pain appearing to arise in a location that does not correspond to original source
Cardiac: crushing chest pain that radiates to neck and left arm
MSK: sharp and stabbing pains
Diaphragm: shoulder-tip pain
53
List respiratory and non-respiratory causes of chest pain
Respiratory causes: pleuritis, PE, pneumothorax, malignancy, infection, rib fracture
Non-Respiratory causes: MI, pericarditis, dissecting aneurysms, valve disease, oesophageal rupture, GORF, panic and self-inflicted
54
Explain what is meant by dyspnoea, the clinical assessment and main causes
Dyspnoea: SOB reported at inappropriately low levels of exertion, and can be unpleasant and frightening while associated with feelings of impending suffocation
Clinical assessment: often assessed subjectively with grading scales such as Borg
Main causes: airflow obstruction, gas exchange abnormalities, restriction of lung mechanics, myocardial disease, valve disease, pericardial disease, metabolic acidosis and anaemia
55
Explain the three respiratory descriptors (SOB)
Air hunger: hunger for air, starved for air, SOB, breath feels to small
Tightness: heaviness/tightness in chest
Work/effort cluster: breathing requires effort/work or is uncomfortable and feels like heavy exercise
56
Summarise the mechanical, local and systemic defences against pathogens in the airways
Mechanical defences: URtract filtration, mucociliary clearance, coughing
Local defences: antiproteases and alveolar macrophages
Systemic defences: polymorphonuclear granulocytes, complement and antibodies
57
Explain what is meant by BALT
(Bronchus Associated Lymphoid Tissue): samples antigens inhaled through nose and produces antibodies against these
58
Describe acquired pathogenic damage of the immune defences of the airways
Viral infections can lead to destruction of the cilia and tight junctions between epithelial cells, before opportunistic bacteria invade; cilia must regrow, taking weeks, and can regrow as useless compound cilia
59
Explain three congenital defects of cilia
Microtubule abnormalities: abnormal microtubules can lead to non-functional cilia and dextrocardia because these guide cells during embryogenesis (so if dextrocardia identified, check cilia function)
Dynein arm defects: lack of outer dynein arm prevents the cilia from moving even if present - stopping mucociliary clearance
Primary ciliary dyskinesia: lack of nasal nitric oxide appears to cause malfunctioning cilia
60
Explain the common cause of pneumonia, symptoms and the outcome
Pneumonia (acute): streptococcus pneumoniae; coughing, sputum, fever and dyspnoea - inflammation leads to stabbing pleuritic chest pain; airways not always scarred and some effort can be made to clear infection
61
Explain the changes seen in bronchiectasis, how this may affect response to infection and possible treatment
Airways become scarred, widened and inflamed with thick mucous that the patient will struggle to clear; pockets of mucous form and harbour bacteria that can multiply without clearance leading to chronic infection - ability to clear mucous chronically damaged, so cannot clear infections (easily); physio to empty the phlegm can prevent bacteria pooling and limit infection/inflammation
62
Describe the effect of chronic inflammation on ability to tackle respiratory infection
Neutrophils secrete proteases to destroy microbes during inflammation and infection, and normally this is balanced by anti-proteases in the airwaysDuring chronic inflammation, the number of neutrophils is so large that the anti-proteases are overwhelmed leading to increased free proteases causing damage to the airway epithelia (which in turn makes it easier to be infected, creating a vicious cycle)
63
Recall the differences in pathogenesis between acute and chronic lung infections e.g. pneumococcal pneumonia vs bronchiectasis
In chronic infections the ability to clear mucous is chronically damaged and so re/co-infection is common
64
Define hypersensitivities and how these can be (initially) classified
Hypersensitivity: exaggerated response to a foreign substance - can be immunological or not
Immunological (Allergy): exaggerated immunological response to a foreign substance (allergen) which is inhaled, swallowed, injected or placed on the skin/eye
Non-Immunological: can be due to intolerance, enzyme deficiency or pharmacologically based
65
Describe how allergies may be separated, define atopy, and state the names given to atopies of the upper airways, bronchi and alveoli
Immunological hypersensitivity: can be further separated to those that are IgE-mediated (atopic disease) and those that are not (e.g. Farmer's lung)
Atopy: hereditary predisposition to produce IgE antibodies to common allergens - e.g. Allergic rhinitis and asthma
Location: upper airways = allergic rhinitis, bronchi = asthma, alveoli = allergic alveolitis
66
Describe the immunological mechanism of allergic rhinitis
1) Allergens pass over epithelium in the airways and are captured by dendritic cells 2) Dendritic cells migrate to lymph nodes and stimulate TH cells to differentiate to TfH (using IL4) and TH2 cells (using IL9) that activate B-cells and mast cells respectively 3) TfH cells stimulate B-cells to become plasma cells that secrete allergen specific IgE antibodies that bind to FcE receptors on mast cells 4) When the allergen cross links IgE antibodies on mast cells, degranulation occurs leading to histamine release
67
Describe the immunological mechanism behind extrinsic allergic alveolitis
1) Small allergenic particles penetrate distal airways and enter alveoli, then interstitium2) Particles are captured by antibodies in the interstitium to form antigen-antibody complexes 3) Complement and immunological cascades are triggered and lymphocytes are recruited
68
Recall the epidemiology and aetiology of allergic airways diseases
Epidemiology: allergic rhinitis affects up to 25% of the population and asthma approx. 10%, yet the conditions are very heterogeneous
Aetiology: food allergies are present from birth but chronic exposure over several seasons is needed to develop allergic rhinitis; common allergens include dust mites, pets, cockroaches, tree pollen and grass pollen
69
Recall treatments for allergic airway diseases
Allergen avoidance: e.g. Staying away from cats
Anti-allergic medication: e.g. Antihistamines and steroids
Immunotherapy: desensitisation to allergens in severe cases
70
Describe the mechanism of action of immunotherapy
Subcutaneous/sublingual exposure to traces of the allergen leads to desensitisation because TH cells become Tregs that inhibit TfH cells, stopping the producting of IgE antibodiesThey can also cause B-cells to become Bregs that inhibit B-cells or become plasma cells that produce IgG/A antibodies that compete for allergen binding with IgE, reducing the hypersensitivity response
71
Define pulmonary and alveolar ventilation
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Pulmonary ventilation (Vpulm): volume of air inhaled per minute (minute ventilation / VE)
Alveolar ventilation (Valv): volume of air reaching the respiratory zone per minute (calculated by subtracting the physiological dead space from the tidal volume)
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72
State what is meant by lung volumes and capacities, and the factors that may affect each
Volumes: are discrete and do NOT overlap
Capacities: sums of volumesFactors Affecting:- Body size (height/shape - not obesity)- Sex- Disease - Age (decreases)- Fitness
73
Define tidal, inspiratory reserve, expiratory reserve and residual volumes
"
Tidal Volume: volume per breath (increases during exercise)
Inspiratory Reserve Volume: extra space in the lungs after normal inspiration available for inspiration
Expiratory Reserve Volume: extra space after normal expiration to force expiration
Residual Volume: anatomical limitation prevents complete exhalation (closed airways are bad airways and cannot ventilate)
"
74
Define vital, functional residual and inspiratory capacity
"
Vital capacity: how much air can be adjusted - useful air
Functional residual capacity: amount of air left in lungs after normal expiration
Inspiratory capacity: amount of air that can be forcibly inhaled from normal breathing
"
75
Describe how lung volumes may change in restrictive and obstructive airways disease
Restrictive: normal rate of exhalation but reduced FVC (and \/ IRV, ERV, RV and TV)
Obstructive: reduced rate of exahlation and markedly reduced FVC (increased residual volume with \/ IRV, ERV and TV)
76
Compare the changes in lung volumes seen in restrictive and obstructive disease
Both have a decreased IRV, ERV and TV, yet the rate of exhalation is only decreased in obstructive, and the residual volume is larger
77
Define anatomical, alveolar and physiological dead space and their normal volumes
Anatomical Dead Space: Capacity of the airways incapable of undertaking gas exchange; usually the conducting zone - the first 16 generations of airways (150ml) - e.g. Nose, pharynx, larynx, trachea, bronchi and bronchioles
Alveolar Dead Space: Capacity of the airways that should be able to undertake gas exchange but cannot (e.g. hypoperfused alveoli); usually the non-perfused parenchyma, which should be 0ml in adults
Physiological Dead Space: Sum of the alveolar and anatomical dead space; i.e. Should be 150ml in adults
78
Describe how dead space may be artificially increased or decreased
Increase: snorkelling/anaesthetic circuits
Decreased: tracheostomy/cricothyrotomy
79
Explain regional differences in ventilation and perfusion
Lung Apex: alveoli are stretched by gravity due to a greater transmural pressure, so need a greater pressure to inflate (less compliant and perform less ventilation); simultaneously, blood is pulled downwards, achieving a lower intravascular pressure, causing reduced perfusion
Lung Base: alveoli are squashed and so can inflate more, performing more ventilation; simultaneously blood is pulled downwards to produce a higher intravascular pressure, increasing perfusion of the parenchyma
80
Describe ventilation perfusion matching and where wasted ventilation and perfusion occur
Ventilation perfusion matching: perfusion and ventilation both increase from apex to base, but perfusion does so at a greater rate
Wasted ventilation: occurs at the apex because perfusion cannot meet the demands of the ventilation supplied
Waster perfusion: occurs at the base because ventilation cannot meet the demands of the blood perfused
81
Explain the ventilation-perfusion ratio (V/Q)
V/Q ratio would be 1 if matched, but gravity means changes regionally (calculated as alveolar ventilation/cardiac output) - averages approx. 0.84 in a healthy lung
82
Contrast the pulmonary and bronchial circulation
Pulmonary Circulation: blood supplied to gas exchange surface for oxygenation
Bronchial Circulation: supplies the parenchyma
83
Contrast pulmonary and systemic circulation
- Wall thickness:lumen ratio is smaller in pulmonary arteries so they are more compliant (stops pulmonary hypertension)- Right ventricle thinner to reduce force- Lower resistance
- 0.5L blood compared to 4.5L- 15% of normal pressure
84
State the three functions of the pulmonary circulation
Gas exchange: pulmonary transit time = 0.75s, with CO2 leaving and O2 entering (or CO/anaesthetics/etc.)
Metabolism of vasoactive substance: endothelial cells express ACE to convert AGTI to AGTII (vasoconstrictor) and break down bradykinin (vasodilator) allowing for vasoconstriction
Blood filtration: emboli (e.g. Air bubbles/ruptured fatty plaques/venous thrombosis) are caught in the pulmonary vessels, filtering out before reaches systemic arteries (can break down) - if large will be local perfusion obstruction
85
Explain the effect of increasing cardiac output on pulmonary vascular resistance
Pulmonary circulation is low resistance, high capacity circuit (at resting Q = 5L/min) - increased Q should increase MAP and pulmonary oedema and reduce function BUT arteries distend due to greater compliance and perfusion to hypoperfused beds (towards the apex) increases, leading to negligible MAP change and minimal fluid leakage
86
Explain the effect of increasing ventilation on pulmonary vascular resistance
"Inspiration compresses alveolar vessels (compressible as no cartilage so as alveolar size increases compresses) and expiration compresses extra-alveolar vessels (thorax decreases in volume to pinch outside) - so when really full or empty then resistance increases
"
87
Explain the effect of hypoxaemia on pulmonary vascular resistance
Systemically causes vasodilation but in pulmonary circulation causes vasoconstriction (O2 sensitive K+ channels close, decreasing the efflux of ions and increasing membrane potential until depolarisation and VSMC contraction) - stops blood flow through unventilated alveoli to match ventilation and perfusion
88
Compare beneficial and pathological impacts of hypoxic pulmonary vasoconstriction
Beneficial: during foetal development to increase resistance in pulmonary circuit, and hence increase flow through shunts (first breath increases alveolar PO2 and dilates pulmonary vessels
COPD: reduced alveolar ventilation and air trapping means all lung vessels constrict leading to pulmonary hypertension, right ventricular hypertrophy and CHF
89
List the forces controlling the production of interstitial fluid in the lungs, and the net movement
Plasma hydrostatic pressure: changes from arterial to venous end of capillaries (highest at very start of capillary - decreasing to venule end)
Interstitial hydrostatic pressure: negligible or negative pressure
Plasma oncotic pressure: should have a lot of protein in blood and less outside, so drawing fluid into vessel
Interstitial oncotic pressure: should have soluble ECM molecules drawing fluid out
Net movement: should be approx. 1mmHg out, and steady fluid accumulation controlled by lymphatics, and if production exceeds maximum clearance then will produce oedema
90
Describe the effects of mitral valve stenosis, liver failure and metastatic breast cancer on pulmonary oedema
Mitral valve stenosis: plasma hydrostatic pressure increases because pressures back up through pulmonary circulation, increasing pressure; causes net accumulation of fluid that exceeds lymphatic capacity leading to oedema and SOB on exertion
Liver failure: liver synthesises plasma proteins, so reduced plasma oncotic force means reduced return to vessels and oedema development
Metastatic breast cancer: normal fluid accumulation but compromised lymph clearance will lead to the development of oedema
91
Explain pulmonary shunting and give anatomical examples
Pulmonary shunts: circumstances leading to the bypassing of the respiratory exchange surfaces (more beneficial in utero as not being ventilated so wastes blood) Bronchial circulation: blood from left side of the heart supplies the parenchyma but drains back to pulmonary veins to re-enter left side of heart
Foetal circulation: in utero blood bypasses non-ventilated lungs as beneficial using the foramen ovale (RA to LA) and the ductus arteriosus (Pulmonary arteries to aortic arch)
Congenital defects: atrial septal defect (/patent foramen ovale) or ventricular septal defects lead to blood mixing across the septa
92
Describe the ducts present in feotal circulation
In utero blood bypasses non-ventilated lungs as beneficial using the foramen ovale (RA to LA) and the ductus arteriosus (Pulmonary arteries to aortic arch)
93
Describe the planes used in ultrasonography
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Axial/transverse plane: right of pt = left on image
Longitudinal/coronal plane: cranial left, caudal right
Paracoronal/parasagittal plane: useful for thoracic US to eliminate rib artefacts
Longitudinal/sagittal plane: cranial left, caudal right
"
94
Differentiate the use of 3.5MHz and 7-12MHz probes for ultrasonography
3.5MHz probe: lower res but increased depth of view - used for deep organs and diaphragm; curved array produces a fan of ultrasound beams to get round the ribs
7-12 MHz probe: smaller with flat surface (linear array), that produces higher res images with a limited depth of view
95
Recall the normal appearance of the lung and ribs on ultrasound
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Normal lung anatomy: visceral and parietal pleura visible on US - echogenic line represents both pleura, and will naturally have some bumps and move slowly/smoothly back and forwards underneath chest wall; artefacts will be present below echogenic lung
Ribs: placing probe across ribs will lead to indentations - form black shadows as all sound reflected "
96
Explain the appearance of comet tails on thoracic ultrasounds
'B Line artefacts': represent interlobular septa - run perpendicular to the lung surface (interlobular septa are the boundaries between secondary pulmonary lobules)
97
Explain the use and normal appearance of M-mode ultrasound
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M-Mode ultrasound: 1D display of motion of echo-producing interfaces displayed against time
Normal M-Mode: should be the sea shore sign; lung pleura should look striated and lung sandy while chest wall should be comprised of straight lines "
98
List usages of a thoracic ultrasound
Thorax US usage:- Detect pleural effusion and guide drainage - Differentiate sub-pulmonary from sub-phrenic fluid - Assess tumour invasion of chest wall/pleura - Guide pleural/lung biopsy - Pneumothorax identification - white line of pleura will disappear - Assessment of respiratory muscle function
99
Describe the appearance of a pleural effusion on a thoracic ultrasound
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Pleural effusion: only a trace of black should exist between lung edge and chest wall, but in a larger pleural effusion, several cm of fluid can accumulate (volume in ml = 200 * distance on US) - if very large, compression makes the lung look solid and not like lung tissue
Small pleural effusion: notice the black region between the chest wall and echogenic line
Large pleural effusion: the lung is compressed to a small size and appears solid "
100
Explain the use of a sniff test on a thoracic ultrasound
Sniffing stimulates phrenic nerve to cause rapid caudal movement of the diaphragm (if damaged then will cause paradoxical cranial movement)
101
Describe the respiratory quotient and state the normal value
Respiratory Quotient/Respiratory Exchange Ratio: CO2 production/oxygen consumption - usually = 1
102
Explain the use of metabolic equivalents and give examples
Oxygen requirements: sat at rest - O2 consumption roughly 3.5ml/min/kg - equal to 1 metabolic equivalent
Metabolic equivalents: standing = 1.5, walking = 2, running > 7
103
Explain the muscle response to exercise
Stored energy (ATP, PCr) used to generate muscular contraction; inorganic phosphates, ADP and creatine drive oxidative phosphorylation while Krebs/glycolysis increases; oxygen consumption at muscle increases, and initially CO2 production rises slowly (as buffered), but then rises to match O2
104
Explain the circulatory response to exercise
Q increases linearly with intensity until plateaus as maximum reached, alongside HR and oxygen consumption - exercise limited by cardiac output; when HR too fast, filling time in diastole reduced, which reduces SV after a peak
105
Explain the pulmonary response to exercise
VT increases with ventilation up to a peak where plateaus, and breathing frequency increases - will breathe at half vital capacity in exercise (increase further not as efficient); VQ matching at rest not ideal, but in exercise increases
106
Describe the Bohr effect
As pH increases, Bohr shift of ODC to right so at given PO2 Hb has less affinity to oxygen so offload more to acidotic muscles
107
Descibe the effect of acidosis in exercise
Lactate converted to protons, and is buffered by bicarbonate to increase CO2, increased ventilation allows pH to remain relatively stableWhen [H+] exceeds HCO3- cannot buffer and begin hyperventilation
108
Explain the process of spirometry and typical presentations of obstructive and restrictive lung disease
"
Spirometry: wearing a noseclip, patient inhales to TLC, then exhales as hard and fast as possible for six seconds into vitalograph- Obstructive: much slower exhalation rate, FEV and FVC lower, with lower FEV1:FVC ratio (volume reduced because airways narrowed)
- Restrictive: similar rate but lower FVC, and higher FEV1:FVC ratio (airways ok but volume affected)
"
109
Explain how a flow-volume loop is created
"1) Patient wraps lips round mouthpiece2) Patient completes at least one tidal breath (A&B) 3) Patient inhales steadily to TLC (C) 4) Patient exhales as hard and fast as possible (D) 5) Exhalation continues until RV is reached (E) 6) Patient immediately inhales to TLC (F)
"
110
Draw and label a flow-volume loop
"
Green: tidal breathing - slow and limited
Red: after PEF should be linear rate
Respiratory flow envelope: red and blue lines - demarcates maximum rates "
111
Draw and explain the flow-volume loops in mild and severe obstructive disease and in restrictive disease
""
112
Draw and explain the flow-volume loops fn variable intra- and extra- thoracic obstruction and in fixed airway obstruction
"
Extrathoracic obstruction: blocked inhalation (decreased inspiratory flow rate)
Intrathoracic obstruction: blocked exhalation (decreased expiratory flow rate)
Fixed airway obstruction: blocked inhalation and exhalation reducing flow rate because narrowed airways - blunting both curves"
113
Describe the effect of COPD and restrictive disorders on flow-volume loops
COPD: volume increases as lungs get larger and coving occurs as smaller airways offer lower flow rates - when severe the capacity decreases further and coving increases
Restrictive disorders: operating at lower volumes and less access to air, with normal/slightly lower PEF peak - filling not moving gas problem
114
List the most common causes of lung cancer
75% attributable to smoking, and in non-smokers usually asbestos, radiation (radon/therapeutic), genetic predisposition or heavy metal exposure (chromates, arsenic, nickel)
115
Describe the development of a lung carcinoma
Multistep accumulation of mutations that cause disordered growth, loss of cell adhesion, invasion of tissue and angiogenesis, occurring in epithelial and stem cells; different pathways for different tumours, and early stages may be reversible
116
Describe the local complications of lung tumours
- Bronchial obstruction: collapse of distal lung leading to SOB and infections/abscesses/pneumonia 2/2 impaired drainage - Invasion of local structures
- Inflammation of pleura/pericardium: leads to pleuritis/pericarditis with breathlessness and cardiac compromise
117
Describe the systemic effects of lung tumours
If metastasises to brain can cause fits, lumps in skin, deranged LFTs if liver and pain/fractures in bones
118
Contrast between benign/malignant and small/non-small cell tumours
Benign lung tumours: do not metastasise, cause local complications e.g. Chondroma
Malignant lung tumours: potential to metastasise, with variable clinical behaviour
Non-small cell: includes squamous cell carcinoma, adenocarcinoma and large cell carcinomas
Small cell: 20% of tumours that grow faster and more aggressively
119
Describe the development and prognosis of squamous cell carcinomas
"
Squamous cell carcinoma: carcinoma of tough epithelium that usually lines skinNormal ciliated epithelium becomes irritated by smoke and undergoes metaplasia to become squamous cell epithelia without cilia - more resistant to damage but no cilia to move mucous; dysplasia and disordered growth occurs as mutations are accumulated and becomes carcinoma in situ
25-40% of pulmonary carcinoma, closely associated with smoking; traditionally central and arising from bronchial epithelium but recent increase in peripheral SqCC; local spread and metastasise late
"
120
Describe the development, prognosis and treatment of adenocarcinomas
Glandular epithelium tumoursDevelops in interstitium and peripheral airways; proliferation of atypical cells along alveolar walls; increase in size and eventually become invasive; adenocarcinoma-in-situ acquire invasive phenotype before invading local tissue and stroma - if can excise early lesions then will cure patient
121
Describe large-cell carcinomas
Poorly differentiated tumours composed of large cells, with no histological evidence of glandular/squamous differentiation (on EM may show evidence of glandular/squamous/neuroendocrine differentiation)
122
Describe small-cell carcinomas
20-25% tumours, closely associated with smoking, and turn over rapidly so very chemosensitive; present with advanced disease and often with brain/liver/bones mets so have abysmal prognosis and die within 18mo
123
Compare the prognosis of small and non-small cell tumours
Small Cell: 2-4 months untreated, 10-20 months treated (chemoradiotherapy needed)
Non Small Cell: Stage 1 = 60% 5yr survival, Stage 4 = 5% 5yr survival
124
Explain the use of FDG-PET-CT for lung cancer diagnosis
Radio-labelled glucose actively taken up by rapidly dividing cancer cells; lung and lymph node tissue should not take up, so if have, then cancer probably spread - activity seen on CT and can be used to see spread
125
Explain the use of trans-thoracic CT biopsy for lung cancer
Needle to lung tissue inserted under CT guidance; real time and high sensitivity yet risk of pneumothorax and bleeding
126
Describe the use of cytology and histology in the diagnosis of lung cancer
Cytology: sputum, bronchial washings, pleural fluid and endoscopic fine needle aspiration can be sampled to identify cells that may be cancerous
Histology: can do biopsy using bronchoscopy, CT guided biopsy, or mediastinal lymph node biopsy (for staging - surgically); can be done during operation to see if malignant within 15 minutes
127
Describe the use of TNM staging
Tumour: TX if immeasurable, T0 if not found, T1-4 if measurable, with a higher number corresponding to a larger size
Nodes: NX if immeasurable, N0 if none affected, N1-3, with a higher number corresponding to more affected nodes
Metastases: MX if immeasurable, M0 if no spread, M1 if has metastasised
128
Explain what is meant by a paraneoplastic syndrome with examples
Paraneoplastic syndrome: syndrome of signs and symptoms that are not due to the local presence of cancer cells, rather are a response to humoral factors such as hormones/cytokines secreted by the tumours or as part of an immune response Examples:- Small cell lung cancers may secrete ectopic ACTH causing Cushing's, or ADH leading to water retention - Squamous cell carcinomas may secrete PTH causing hypercalcaemia
129
Summarise the risk factors and recall the pathology of mesothelioma
Mesothelioma risk factors: asbestos exposure is the main risk factor, with increasing exposure linked to increased risk (some genetic component exists too)
Pathology: mesothelium is a layer of cuboidal epithelial cells lining the pleural cavity, and deposition of asbestos fibres in the lung parenchyma can cause penetration of the visceral pleura and development of plaques and tumour development
130
Explain primary ciliary dyskinesia
AR mutation (45 known) that impacts on ciliary function; dynein arms are absent, causing cilia to become static so mucous is not moved and cleared; will get bronchiectasis and respiratory failure
131
Explain the effect of congenital bronchial cartilage defects and laryngomalacia
Congenital bronchial cartilage defects: normally incomplete rings with irregular plates, but can be malacic (floppy) in generalised or localised (occur due to other developmental issue) fashion - always check CVD status
Laryngomalacia: omega shaped epiglottis with folds that collapse on inspiration - severe airway obstruction
132
Describe agenesis, aplasia and hypoplasia of the lung
Agenesis: complete absence of lung and vessel - rare and associated with other conditions
Aplasia: blind ending bronchus with no lung or vessel
Hypolasia: bronchus and rudimentary lung present but all elements reduced in size and number; relatively common and 2/2 other (physical) factors such as lack of space intra/extrathoracically - can be corrected with in utero surgery
133
Describe cystic pulmonary airway malformation
Mostly diagnosed on antenatal ultrasound; lethal so won't survive but usually seen well; normal blood supply with defect in pulmonary mesenchyma causing abnormal differentiation in early weeks
134
List the in-utero phases of lung development and the timings
1) Embryonic phase: 0-7 weeks
2) Pseudoglandular phase: 5-15 weeks
3) Canalicular phase: 16-27 weeks
4) Saccular/Alveolar phase: 28-40 weeks
135
Describe the embryonic phase of lung development that occurs between {{c1::0-7}} weeks
Asymmetric branching occurs to produce 3 lobes on the right and 2 on the left
136
Describe the pseudoglandular phase of lung development that occurs between {{c1::5-17}} weeks
Branching morphogenesis of airways to the mesenchyme, with pre-acinar airways all present by 17 weeks; development of cartilage, glands and smooth muscle continues to canalicular phase
137
Describe the canalicular phase of lung development that occurs between {{c1::16-27}} weeks
Peripheral airspaces enlarge, with thinning of epithelium by underlying capillaries to allow gas exchange, but forming blood gas barrier required in post-natal life; epithelium differentiates to type I (thin)/II (surfactant - surface tension and allows re-expansion) cells and surfactant detectable at 24-25 weeks - babies become viable at 24 weeks gestation due to surfactant
138
Describe the saccular/alveolar phase of lung development that occurs between {{c1::28-40}} weeks
Alveolar walls form first as saccule walls with double capillary networks, before forming secondary septa then alveolar walls as the capillaries coalesce to form one sheet, with elastin in the wall produce by myofibroblasts
139
State the factors driving morphogenesis of the lungs
Lung buds drive process, with progenitor multipotent cells at the tip that differentiate to a range of lung cells based on chemical environment, physical activity and growth factors; communication between the mesenchyme leads to balanced growth factor production
140
List the inductive and inhibitory factors for lung morphogenesis and the role of vasculogenesis
Inductive factors: FGF (morphogenesis) and EGF (epithelial proliferation and differentiation)
Inhibitory factors: TGFbeta (matrix synthesis and inhibition of epithelium proliferation) and retinoic acid (inhibits branching)
Vasculogenesis: airways act as a structural template for capillary networks to form
141
Summarise the lung growth and development in the postnatal period
The number of alveoli increases until puberty/adulthood with surface area increasing until body growth is complete; arteries, veins and capillaries increase alongside the alveoli
142
Explain the cardiorespiratory changes that occur at birth
At birth: lungs have a small volume, related to body weight, with all airways present and differentiated, and most arteries/veins but only 33-50% of alveoli present Mechanisms to increase flow after birth:- Expansion of arteries dilate arteries to increase blood flow- Expansion stimulates release of vasodilators such as NO/PGI2
- Vasoconstrictors present during foetal life - if not inhibited then will get pulmonary hypertension - Direct effect of oxygen on smooth muscle cells
143
Summarise the oxygen cascade
"
O2 cascade: describes decreasing oxygen tension from inspired air to respiring cells; Fick's law says flow rate proportional to pressure gradient - structural disease reduces the area, fluid in alveolar sacs increases thickness and hypoxic gas reduces gradient Oxygen in air at highest partial pressure, decreasing from 21.3kPa (air) to 13.5 in alveoli, 13.3 in tissues to 5.3 in veins "
144
Describe the challenges to the oxygen cascade
V/Q matching: if blockage in respiratory tree and are not ventilating but are perfusing then will not gain oxygen and will drop
Diffusion capacity: thickness of exchange surface will reduce oxygen gain
Cardiac output: need high Q to move blood to tissues
145
Describe the effects of altitude on the oxygen cascade
"
| Altitude cascade: reduces in ambient pressure reduces oxygen and gradient - harder to maintain homeostasis "
146
State the differences between normal Hb and foetal haemoglobin and myoglobin
Foetal haemoglobin: gamma chains give greater affinity than HbA to extract oxygen from placental blood
Myoglobin: much greater affinity than HbA to extract oxygen from circulating blood for storage
147
Describe methaemoglobin and the impact of methylene blue
Methaemoglobin: has Fe3+ not Fe2+; exists as <1% of total Hb in body - does not bind oxygen, constantly in equilibrium with Hb, switching between Hb and MetHb
Methylene blue: increases haemoglobin from methaemoglobin
148
Describe oxygen delivery in blood with NO haemoglobin
Oxygen can diffuse into blood and be carried at 16mL min-1, whereas the VO2 required is 250mL min-1 so Hb is needed
149
Describe the structure of haemoglobin
Haemoglobin: monomers consist of Fe2+ ions at centre of tetrapyrrole porphyrin ring connected to globin protein chain, covalently bonded at proximal histamine residue (Has two Hba subunits and two of Hb beta/sigma/gamma depending on type)
150
Describe the affinity and shape of haemoglobin as oxygen binds
"
Affinity: increases exponentially as oxygen binds (max 4) - cooperative binding
Change in shape on binding: middle of Hb becomes binding site for 2,3-DPG (associated with metabolic activity) when 4 O2 bind; upon binding, pushed into tense shape (tightens) to eject oxygen - allosteric behaviour "
151
Describe how carbon dioxide reacts within blood
```
Carbon dioxide: enters blood and reacts slowly with water to form carbonic acid which can dissociate: CO2 + H2O -> H2CO3 -> H+ + HCO3- - CO2 IS ACID (non-enzymatic)
Carbonic anhydrase (in Hb): increases formation of H2CO3 by 5000x - CO2 can move into erythrocytes
```
152
Describe how CO2 is transported within the blood and the role of the chloride shift
CO2 Transport in Blood: 1) Dissolves in solution 2) As bicarbonate 3) Also binds to Hb (amine end of the globin chains, 1 Hb = 4 O2 and 4 CO2)
Chloride shift: negative chloride ions enter RBCs to maintain RMP with AE1 transporters
153
Recall Dalton, Fick and Henry's Laws
Dalton's Law: pressure of a gas mixture is equal to the sum of the partial pressures of all the gases in it
Fick's Law: molecules from regions of high concentration to lower concentration at a rate proportional to the concentration gradient, the exchange surface area, and the diffusion capacity of the gas; it is inversely proportional to the thickness of the exchange surface
Henry's Law: At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid
154
Recall Boyle and Charles' Laws
Boyle's Law: At a constant temperature, the volume of a gas is inversely proportional to the pressure of that gas
Charles' Law: At a constant pressure, the volume of a gas is proportional to the temperature of that gas
155
Explain the normal shape of the oxygen dissociation curve
"Not linear to ensure that high saturation occurs in lungs but that in systemic circuit a lot of oxygen can be unloaded when really needed, but at rest only remove ~25% of oxygen
"
156
Define P50 and state what may cause a left/right shift of the ODC
```
"
P50: partial pressure of oxygen when HbO2 = 50%
Left shift (increased affinity): hypothermia, alkalosis, hypocapnia, decreased 2,3-DPG
Right shift (decreased affinity): hyperthermia, acidosis, hypercapnia, increased 2,3-DPG
```
"
157
What 4 things affect P50?
Temp, pH, CO2 and 2,3-DPG
158
State what may shift the ODC upwards or downwards and what this means
"
Upwards shift: polycythaemia (Increased oxygen carrying capacity)
Downwards shift: anaemia (Impaired oxygen carrying capacity)
Down and leftwards: decreased capacity and increased affinity results from increased HbCO (carboxyhaemoglobin)
"
159
Describe the shape of the CO2 dissociation curve
"
CO2 dissociation curve: practically linear, with slightly higher concentration in venous blood than arteries; the more oxygenated the Hb, the less CO2 accepted
"
160
Define alkalaemia, acidaemia, alkalosis and acidosis
Alkalaemia: refers to higher than normal blood pH
Acidaemia: refers to lower than normal blood pH
Alkalosis: circumstances that will decrease [H+] and increase pH
Acidosis: circumstances that will increase [H+] and decrease pH
161
State the normal ranges on an ABG for pH, PCO2, PO2, HCO3- and base excess
""
162
Describe compensatory mechanisms for respiratory acidosis
Acute phase: CO2 moves into erythrocytes, combines with H2O in presence of carbonic anhydrase to form bicarbonate, which moves out of cell by AE1 transporter; increased bicarbonate leads to raised base excess, shifting equilibrium backwards to carbonic acid and reducing [H+]
Chronic phase: increases bicarbonate reabsorption in kidneys to stabilise pH
163
Describe compensatory mechanisms for respiratory alkalosis
Reduces bicarbonate absorption from nephrons and increases secretion in collecting duct, causing more carbonic acid dissociation, reducing base excess
164
Describe compensatory mechanisms for metabolic acidosis
Increasing ventilation rate to increase diffusion gradient and reduce PCO2, causing shift to left on equilibrium, forming carbonic acid, and then CO2
165
Describe compensatory mechanisms for metabolic alkalosis
Reducing ventilation rate to increase arterial PCO2 drives equation to right to increase protons and bicarbonate
166
Describe the steps to interpet an ABG
1) pH?2) PaCO2?3) BE?4) PaO2?5) Evaluate acid-base status6) Evaluate oxygenation
167
Define type 1 respiratory failure
Hypoxic respiratory failure with normal CO2 and low O2; acute problem due to a V/Q mismatch - e.g. PE/foreign body/pneumonia
168
Describe type 2 respiratory failure
Hypercapnic respiratory failure with both high CO2 and low O2; chronic and due to alveolar hypoventilation - e.g. COPD/obesity/pulmonary fibrosis
169
Define the Henderson-Hasselbach equation
pH = pK + log10([HCO3-]/[CO2])Links pH of blood to HCO3- and CO2 concentrations
170
State the equilibrium that the acid base status depends upon
H2O + CO2 <-> H2CO3 <-> H+ + HCO3-
171
Describe the changes in atmospheric oxygen at altitude and the initial detection
Still 21% O2 but at lower partial pressure, decreasing PA/PaO2, which activates peripheral chemoreceptors (as opposed to central control using CO2)
172
Describe the neural response to decreased PaO2
- Increased SNS outflow increases ventilation to increase alveolar oxygen and oxygen loading - Increased SNS will increase Q (HR/SV) to increase oxygen loading (and tissue delivery)
173
Describe the hormonal response to decreased PaO2 at altitude
Low blood oxygen increases erythropoietin production, increasing RBC production and oxygen loading
174
Explain the main sequence of changes in response to decreased PaO2 at altitude
1) Peripheral chemoreceptors activated2) SNS increases ventilation and HR/Q to increase oxygen loading3) Hyperventilation = hypocapnia, reducing the central drive to breathe and decreasing oxygen loading4) pH increases shifts ODC left to further reduced oxygen unloading5) Alkalosis detected by carotids and increases bicarb secretion to normal ODC and increase oxygen unloading
175
Describe the metabolic response to decreased PaO2 at altitude
Oxidative enzyme/mitochondrial numbers increase to allow for greater oxygen utilisation to produce energy; small 2,3-DPG increase, causing shift to right and increased oxygen unloading
176
Describe prophylactic measures against altitude sickness
Acclimation: stimulated by artificial environments to lead to artificial acclimatisation (e.g. Hyperbaric chamber/breathing hypoxic gas)
Acetazolamide: carbonic anhydrase inhibitor, accelerates slow renal compensation to hypoxia induced hyperventilation
177
Describe the movement of the oxygen dissociation curve in the lungs and tissues
Pulmonary circulation: low CO2 in alveoli = decreased [H+] = left shift so Hb affinity increases and O2 is absorbed into the Hb from the alveoli
Systemic circulation: high CO2 from respiration = increased [H+] = right shift so Hb affinity increases and O2 is released into the tissues from the Hb
178
Describe the mechanical forces leading to inspiration and expiration
Inspiration: intercostals and diaphragm contract to pull parietal pleura away from the visceral pleura to widen pleural space and decrease the intrapleural pressure; pressure gradient between alveoli and pleural space widens causing inflation, decreasing intra-alveolar pressure, so air flows down pressure gradient to alveoli
Expiration: intercostals and diaphragm relax to pull parietal pleura towards the visceral pleura to narrow the pleural space and increase the intrapleural pressure; pressure gradient decreases, causing deflation, recoil and expulsion of air from the alveoli down a pressure gradient
179
Recall the cellular layers separating alveolar air from blood, and explain how alveoli and airways resist collapse
Cellular layers: 1 cell thick epithelium (alveolar) and 1 cell thick endothelium (capillary)
Resisting collapse: achieved using surfactant and elastic tissue in the interstitium
180
Describe the anatomy and innervation of the nasal cavities (not the sinuses)
Nasal septum: divides the two halves (largely cartilage - lined by olfactory mucosa)
Olfactory mucosa: very sensitive and innerfaved by the trigeminal nerve
Olfactory bulb: present at the top, and supplied by the olfactory nerves
181
Describe the location of the paranasal air sinuses
"Frontal sinus: anteriorly in frontal bone above eye
Ethmoid sinuses: superiorly
Sphenoidal sinus: posteriorly in sphenoid bone below pituitary gland
Maxillary sinus: laterally
"
182
Describe the roles of the sinuses and concha in the nasal cavity
Sinuses: lighten the skull and protect brain
Concha: increase surface area for nasal mucosa to condition air before reaching lungs
183
Differentiate the regions of the airways above the level of the trachea
"
Pharynx: top of nasal cavity to opening of the larynx; can be divided to three areas: nasopharynx (nasal cavity to end of soft palate), oropharynx (soft palate to epiglottis) and laryngopharynx (epiglottis to opening of airway)
Larynx: from opening of airway to trachea"
184
Describe the cartilages of the larynx
"All cartilage hangs from the hyoid bone, to which the epiglottis is attached
Thyroid cartilage: hangs from the hyoid bone using a membrane to protect the thyroid glands
Cricoid cartilage: hangs from the thyroid cartilage using the cricothyroid ligament
"
185
Describe the anatomy of the trachea, tracheobronchial tree and the bronchi
Trachea: horseshoes of cartilage embedded in walls, but are deficient posteriorly; lined by same respiratory epithelium, with trachealis muscle posteriorly to join horseshoe
Tracheobronchial Tree: trachea divides at carina at angle of Louis to right and left primary bronchi (outside the lungs); as enter lung, branch to form the lobar bronchi (secondary bronchi)
Bronchi: held open by cartilage horseshoes and plates, with surface tension reduced by surfactant
186
Where are objects most likely to become lodged if inhaled?
Inferior lobe of the right lung (more vertical)
187
Describe the conditions resulting from canncerous invasion of the SVC, oesophagus, airways and nerves
SVC: venous congestion in head/arms
Oesophagus: dysphagia
Airways: haemoptysis
Nerves: Horner's syndrome
188
Describe parasympathetic innervation of the airways
Secretomotor: uses Vagus to produce bronchoconstriction, vasodilation and mucous secretion
Sensory: uses Vagus afferent via the nodose ganglion
189
Recall the mechanisms that can produce bronchodilation in humans and animals
Humans: adrenaline from the adrenal gland and nitric oxide producing pathways
Animals: SNS pathways from C-spine ganglia
190
List the functions of tracheo-bronchial circulation
- Warms inspired air- Humidifies inspired air- Clears inflammatory mediators and inhaled drugs- Supplies oxygen and plasma
191
List the functions or airway smooth muscle
Tone: control airway calibre
Secretion: mediators and cytokines
192
Recall the features and functions of club (clara) cells
Stem cell: regenerate bronchioles
Apical secretory granules: secretion of extracellular fluid
P450 enzymes: xenobiotic metabolism
193
Recall the Law of Laplace for cylinders and spheres
Cylinder: t = pr
Spheres: t = pr/2
194
Describe the immune response seen in asthma
1) Allergen exposure and picked up by dendritic cells
2) Dendritic cells present to TH2 cells
3) TH2 cells release IL4 and IL5
4) IL4 leads to IgE antibody production and mast cell degranulation
5) IL5 leads to eosinophils secreting cytokines and leukotrienes
195
Contrast the immediate and long term responses in asthma
Immediate: bronchospasm and mucous secretion (IgE - narrows airways) - OBSTRUCTIVE
Chronic: increased vascular permeability and immune cell recruitment, leading to inflammatory mediators and scarring/fibrosis - RESTRICTIVE
196
Recall the treatments for asthma
Bronchodilators and corticosteroids
197
Describe the conditions that comprise COPD
Bronchitis: airway mucous hypersecretion due to hypertrophy/plasia of the goblet cells
Emphysema: destruction of elastic alveolar walls by metalloproteinases and elastases released by neutrophils
198
Recall the treatments for COPD
Mucolytics and bronchodilators
199
Recall which of asthma and COPD is reversible, and the cytokines in each
Asthma: reversible; IL4 = IgE; IL5 = eosinophils
COPD: irreversible; IL8 = neutrophil activation
200
State the inhibitors of neutrophil elastase and matrix metalloproteinases
NE: alpha1 antitrypsin
MM: tissue inhibitors
