Respiratory Flashcards

1
Q

What makes up the upper respiratory tract?

A

Nasal cavity
Pharynx
Larynx

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2
Q

What makes up the lower respiratory tract?

A

Trachea
Primary bronchi
Lungs

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3
Q

What are the main functions of the nose in the respiratory tract?

A

Filtration
Defence- cilia take inspired particulates back to be swallowed
Warms and humidifes air

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4
Q

Describe the anatomy of the nose

A

Anterior nares open into enlarged vestibule which is lined with skin and stiff hairs
Turbinates double surface area

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5
Q

What are the 3 turbinates of the nose?

A

Superior meatus
Middle meatus
Inferior meatus

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6
Q

What are the 4 types of paranasal sinuses?

A

Frontal
Maxillary
Ethmoid
Sphenoid
They are pneumatised areas of these bones
They are evaginations of mucous membranes form the nasal cavity

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7
Q

Describe anatomy (location) of frontal sinuses

A

Within frontal bone
Midline septum
Over orbit and across superciliary arch
Supplied by ophthalmic division of nerve V

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8
Q

Describe anatomy (location) of maxillary sinuses

A

In body of maxilla
Pyramidal in shape
Base on lateral wall of nose
Apex at zygomatic process of maxilla
Roof is floor of orbit
Floor is alveolar process
Opens into middle meatus via hiatus semilunaris

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9
Q

Describe anatomy (location) of ethmoid sinuses

A

Between the eyes
Labyrinth of air cells (looks like honeycomb)
Drain into middle meatus by semilunar hiatus
Supplied by ophthalmic and maxillary nerve V

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10
Q

Describe anatomy (location) of sphenoid sinuses

A

Medial to cavernous sinus, carotid artery linked to C3-6
Inferior to optic canal, dura and pituitary gland
Empties into sphenoethmoidal recess, lateral to the attachment of nasal septum
Supplied by ophthalmic nerve V

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11
Q

What is the pharynx?

A

Fibromuscular tube lined with epithelium
Connects back of nose to larnyx

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12
Q

What is at the nasopharynx?

A

Eustachian tube enters into nasopharynx
Inferiorly at soft palate enters to oropharynx
Pharyngeal tonsils on posterior wall

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13
Q

Describe anatomy of oropharynx

A

Back of mouth, soft palate anterior to oro
Palatine tonsils on lateral walls
Inferior to hyoid bone
Palatoglossal folds
Palatopharyngeal folds

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14
Q

Describe the larynx (anatomy and function)

A

Valvular function
Prevents liquids and food from entering lungs
Rigid structure with 9 cartilages
Arytenoid cartilages rotate on the cricoid cartilage to change vocal cords

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15
Q

What are the single laryngeal cartilages?

A

Epiglottis
Thyroid
Cricoid

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16
Q

What are the double laryngeal cartilages?

A

Cuneiform
Corniculate
Arytenoid

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17
Q

Which nerves innervate larynx?

A

Vagus (CNX) splits into superior laryngeal nerve and recurrent laryngeal nerve

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18
Q

What is the role of the superior laryngeal nerve?

A

Provides sensation to larynx (internal) and supplies cricothyroid muscle (external)

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19
Q

What is the role of the recurrent laryngeal nerve?

A

Innervates all muscles in the larynx except cricothyroid
R and L have different courses
Left loops under aorta and ascends between trachea and oesophagus
Right: R subclavian artery, plane between trachea and oesophagus

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20
Q

What is a normal/average minute ventilation?

A

approx 5 litres

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21
Q

What is normal CO amount?

A

approx 5 litres

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22
Q

What is the size of the gas exchange surface of each lung (spread out)

A

20m^2

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23
Q

What are the main airways (biggest to smallest) in the lower resp tract?

A

Trachea
Main bronchi
Lobar bronchi
Segmental branches
Respiratory bronchiole
Terminal bronchiole
Alveolar ducts and branches

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24
Q

What is the structure of the trachea?

A

Runs from larynx to T5
Commences at cricoid cartilage
Oval in cross-sections, incomplete cartilages
Trachealis muscle joins incomplete circuit
Mobile
Sensory innervation from recurrent laryngeal nerve
Arterial supply from inferior thyroid artery

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25
What is the basic structure of the R main bronchus?
1cm-2.5cm long Vertically disposed, shorter than L
26
What is the basic structure of the L main bronchus?
5cm long Longer than R
27
What is the acinus?
Functional unit distal to the terminal bronchiole
28
What are the 2 layers of pleura?
Visceral: applied to lung surface, only autonomic innervation Parietal: applied to internal chest wall, pain sensation
29
Describe the pleura
Visceral and parietal Each a single cell layer Continuous with each other at lung root
30
What happens in acute inflammation to make it appear red and swollen?
Vasodilation of vessels (redness) Exudation of plasma to deliver antibodies (swelling) Activation of biochemical cascades to target bacteria Pain receptors triggered Migration of blood leukocytes into tissue
31
Examples of inflammation-mediated tissue damage in lung
COPD Acute respiratory distress syndrome Bronchiectasis Asthma Interstitial lung disease
32
What is ARDS?
Acute respiratory distress syndrome Respiratory failure from alveoli filling with water and neutrophils Caused by any condition causing inadequate tissue oxygenation (trauma, surgery, pneumonia)
33
Process of acute inflammation
Initiated by epithelial surfaces producing hydrogen peroxide (in tissue), damage causing release of cellular contents Amplified by specialist macrophages Respond to pathogens/ damage by recognising pathogen-associated molecular patterns or damage-associated MPs
34
What cells can amplify acute inflammation?
Specialist macrophages: - Kupffer cells (liver) - Histiocytes (skin and bone) - Dendritic cells - Alveolar macrophages (lung)
35
What recognises pathogens we haven't seen before?
Pattern recognition receptors
36
Types of signalling receptors for pattern recognition
Toll-like receptors Nod-like receptors
37
Types of endocytic receptors
Mannose Glucan Scavenger
38
What are TLRs?
Toll-like receptors Recognise conserved molecular patterns in pathogens Also recognise endogenous mediators of inflammation
39
Describe the alveolar macrophage
93% of pulmonary macrophages Longer lived Arise from circulating monocytes Initially produced in foetus and colonise lungs, mature wave comes from foetal monocytes Removed from lung when exhausted, new macrophages replace throughout life
40
What is macrophage plasticity?
Macrophages can change behaviour to suit environment
41
Describe the neutrophil
70% of all WBCs 100 million turnover a day More made in sepsis Granulocytes Half in blood, half marginated especially in lung Will adhere to wall, then migrate into tissue when needed
42
What do primary neutrophil granules contain?
Myeloperoxidase Elastase Cathespins Defensins
43
What do secondary neutrophil granules contain?
Receptors Collagenase Lysozyme
44
Describe the process of inflammation
Neutrophils adhere to endothelium and transmigrate into tissues Oedema Neutrophils take up and digest bacteria or release granules Apoptosis of neutrophil (taken up by macrophages and removed)
45
Life of a neutrophil from threat to death
Identify threat Activation Adhesion Migration Phagocytosis Bacterial killing Apoptosis
46
What do neutrophil receptors recognise?
Bacterial structures- cell wall, lipids, peptides Host mediators- cytokines, complement cascade, lipids Host opsonins- FcR, CR3 Host adhesion molecules
47
How does neutrophil activation work?
Stimulus response coupling (e.g. proportionate response to threat) Signal transduction pathways involving calcium, protein kinases, phospholipases and G proteins
48
How does neutrophil adhesion work?
Margination from selectins, rolling Integrins mediate firm adhesion Require changes in endothelium and neutrophils Neutrophils flatten out and migrate
49
What can CD18 deficiency cause?
No transendothelial migration Delayed separation of umbilical cord Recurrent severe cutaneous and deep infections
50
What happens in phagocytosis?
Phagocytic cup extended and fuses around bacteria Forms phagosome Fusion with granules forms phagolysome
51
What is generated in bacterial killing?
Reactive oxygen species generated by NADPH oxidase and ATP
52
What is intrinsic defence?
Always present Physical and chemical Apoptosis Autophagy Present anti-viral proteins
53
What is innate defence?
Induced by infection Interferon Cytokines Macrophages NK cells
54
What is adaptive immunity?
Tailored to a pathogen T and B cells
55
What is epithelium?
A tissue composed of cells that line the cavities and surfaces of structures throughout the body Also forms many glands Lies on top of connective tissue, layers are separated by a basement membrane
56
What does respiratory epithelium do?
Moistens and protects the airways Barrier to potential pathogens and foreign particles, preventing infection and tissue injury by action of the mucociliary escalator.
57
Histology of airway epithelium
Nasal cavity and superior pharynx: pseudostratified, mucosa + mucous escalator Pharynx: stratified squamous Lower resp tract: pseudostratified, mucosa Bronchioles: cuboidal Gas exchange surfaces: simple squamous
58
What are the chemical epithelial barriers?
Anti-proteinase Anti-fungal peptides Anti-microbial peptides Antiviral proteins Opsins
59
What is mucus and how is it moved around?
Viscoelastic gel from goblet and submucosal cells Transported from the lower resp tract to pharynx via mucociliary clearance (cilia beat in directional ways to move mucus)
60
What is the role of mucus in defence?
Protects the epithelium from foreign material and fluid loss
61
What is the reason for coughing and sneezing?
Non-immune defence mechanisms
62
What is a cough?
Expulsive reflex that protects the lungs and respiratory passages from foreign bodies
63
What can cause a cough?
Irritants: fumes, dust Diseased conditions: COPD, tumours Infections
64
Which nerves can be involved in triggering a cough?
Afferent nerves: trigeminal, glossopharnygeal, superior laryngeal and vagus Efferent nerves: laryngeal and spinal
65
What is a sneeze?
Involuntary expulsion of air containing irritants from the nose
66
What can cause a sneeze?
Irritation of nasal mucosa Excess fluid in airway
67
Pathway of triggering a sneeze
Receptors in upper tract transduce signals Nerve endings pick up and signals travel through sensory to brain stem Travels on motor neurons to effectors and causes sneeze
68
How does airway epithelium repair itself after injury?
Injury leads to cell spreading and migration Basal cell population is progenitor cell pool (e.g. can turn into club cells, ciliated cells which then become goblets) Proliferating cells regenerate Alveolar type 2 cells can produce proteins and give rise to alveolar type 1 cells
69
What goes wrong in obstructive lung disease?
Obstruction in airway Production of respiratory secretions and pathogenic material that can't be cleared through escalator
70
What is the respiratory pump?
Made up of bones, muscles, pleura, peripheral nerves Generates negative intra-alveolar pressure Moves 5 litres in/out per minute
71
What are the muscles involved in inspiration?
External intercostals Diaphragm, C3,4,5
72
What is dead space in the lung?
The volume of air not contributing to ventilation Made up of anatomic and alveolar components Anatomic deadspace: 150mls (in airways not available for gas exchange) Alveolar deadspace: 25mls
73
How much dead space is in the lung?
Anatomic deadspace: 150mls Alveolar deadspace: 25mls Physiological is total so 175mls
74
What is the pressure of pulmonary circulation?
24mmHg/10mmHg
75
How does alveolar perfusion work?
1000 capillaries per alveolus Each erythrocyte comes into contact with multiple alveoli Capillaries at the most dependent parts of the lung are preferentially perfused At rest: haemoglobin is fully oxygenated 25% of the way through capillary
76
What does alveolar perfusion depend on?
Pulmonary artery pressure Pulmonary venous pressure Alveolar pressure
77
What is hypoxic pulmonary vasoconstriction?
Ventilation and perfusion matched If part of the lung is hypoxic, blood vessels constrict and divert blood away to oxygenated parts of the lung
78
What does PaCO2 mean?
Partial pressure of CO2 in artery
79
What does PACO2 mean?
Partial pressure of CO2 in alveolar
80
What does PaO2 mean?
Partial pressure of O2 in artery
81
What does PAO2 mean?
Partial pressure of O2 in alevolus
82
What does PiO2 mean? And what does it equal?
Pressure of inspired oxygen 21kPa at sea level
83
What does FiO2 mean? And what is it?
Fraction of inspired oxygen 0.21
84
What does V̇A mean?
Rate of alveolar ventilation
85
What does V̇CO2 mean?
Rate of CO2 production
86
What is the equation for PaCO2?
PaCO2 = kV̇CO2 divided by V̇A normally = 4-6kPa
87
How is CO2 carried?
Bound to haemoglobin Dissolved in plasma As carbonic acid
88
What are the physiological causes of a high CO2?
V̇A reduced, increase in minute ventilation, increase in dead space from shallow breathing and ventilation/perfusion mismatch, increase CO2 production
89
What is the alveolar gas equation?
PAO2 = PiO2 - PaCO2 / R R = respiratory quotient, 0.8
90
What are some causes of hypoxia?
Alveolar hypoventilation Reduced PiO2 Ventilation/perfusion mismatching Diffusion abnormality
91
What is the normal pH of arterial blood?
pH = 7.40 (.36-.44)
92
How does acid/base control work in the blood?
Carbonic acid/ bicarbonate buffer CO2 is under respiratory control (rapid) HCO3- is under renal control (less rapid)
93
Equation for carbonic acid equilibrium
CO2 + H2O <-----> H2CO3 <-----> H+ + HCO3-
94
What happens physiologically in respiratory acidosis? (underventilating)
CO2 rises pH will decrease as ratio between CO2 and acid has changed As PaCO2 rises, HCO3- must also rise to keep pH normal
95
What is the henderson hasselbach eqtn for acid/base control?
pH = 6.1 + log10 ( [HCO3-] / [0.03 x PCO2] )
96
What is respiratory acidosis?
increased PaCO2, decreased pH, mild increased HCO3-
97
What is respiratory alkalosis?
decreased PaCO2, increased pH, mild decreased HCO3-
98
What is metabolic acidosis?
reduced bicarbonate and decreased pH
99
What is metabolic alkalosis?
increased bicarbonate and increased pH
100
What is tidal volume?
The volume of air entering or leaving the lungs during a single breath Usually 0.5L resting
101
What is inspiratory reserve volume (IRV)?
The extra volume of air that can be maximally inspired above the typical resting tidal volume 2.5 Litres
102
What is inspiratory capacity?
Max volume of air that can be inspired at the end of a normal quiet expiration IRV + TV 3 Litres
103
What is expiratory reserve volume (ERV)
The extra volume of air that can be actively expired by maximally contracting the expiratory muscles beyond the normal passive expiration at the end of resting TV 1.5 litres
104
What is residual volume?
The minimum volume of air remaining in the lungs even after a maximal expiration Can't be measured with a spirometer as it doesn't move in and out of lungs Average = 1200mL
105
What is functional residual capacity?
The volume of air in the lungs at the end of a normal passive expiration ERV + RV Average value 2200mL- 3Litres
106
What is vital capacity?
Max volume of air that can be moved out during a single breath following a maximal inspiration IRV + TV +ERV 4.5 litres
107
What is total lung capacity?
Max volume of air that the lungs can hold Sum of all Average value = 5700mL- 6L
108
What is forced expiratory volume in 1 sec (FEV1)?
Volume of air that can be expired during the first second of expiration in a VC determination Normally about 80% of VC
109
What is peak expiratory flow?
Single measure of highest flow during expiration Measured via peak flow meter
110
What is gas dilution?
Measurement of all air in the lungs that communicates with the airways Doesn't include gas not communicating Either closed-circuit helium dilution or open-circuit nitrogen washout
111
Different ways to measure lung function/ volume
Total body plethysmography Peak flow Gas dilution Spirometry
112
What is a TLCO test?
Measures how well the lungs take up oxygen from air breathed in Uses helium and CO as CO has high affinity for haemoglobin
113
What does TLCO measure the interactions of?
Alveolar SA and capillary perfusion Capillary volume Haemoglobin concentration Reaction rate of CO and haemoglobin Physical properties of alveolar capillary interface
114
What is an abnormal value of FVC and what does that suggest?
Below 80% Sign of airway restriction
115
What ratio suggests airway obstruction?
Ratio between FEV1 and FVC is less than 70%
116
What are some features of asthma?
Periods of wheeze and shortness of breath Airways obstruction and PEF variation Reduced mid expiratory flows Made better by treatment
117
What are FEV1 and FVC like in asthma?
Normal FEV1 sometimes reduced
118
What are the typical blood gases like for asthma?
Abnormalities in acute asthma attacks, otherwise normal Drop in PaCO2
119
What are some features of COPD?
Progressive Wheeze and shortness of breath on exercise and worse with time Intermittent exacerbations Airways obstruction and lack of PEF variation Reduced mid expiratory flow Poor response to treatment
120
What are the FEV1 and FVC like in COPD?
FEV1 reduced significantly FVC normal or reduced
121
What are the main requirements of respiration?
Ensure haemoglobin is as closes as possible to fully saturated with oxygen Use energy efficiently Regulate PaCO2 carefully
122
Where are the major locations for phasic discharge for breathing?
Pons: pneumotaxic and apneustic Medulla: dorsal respiratory group (predominantly inspiration) and ventral respiratory group
123
What is the central pattern generator?
Located within dorsal and ventral RG Neural network that starts, stops and resets integrator of background ventilatory drive
124
What happens during inspiration?
Progressive increase in inspiratory muscle activation Lungs fill at constant rate until tidal volume reached End of inspiration has rapid decrease in excitation of respiratory muscles
125
What happens during expiration?
Largely passive due to elastic recoil of thoracic wall Active slowing with some inspiratory muscle activity Can become active as well with additional abdominal wall muscle activity
126
Where are the central chemoreceptors and what is their function?
Medulla oblongata (pontomedullary junction) Detect changes in PaCO2 (PaCO2 has 60% influence) Respond to most changes in CO2
127
Where are peripheral chemoreceptors and what is their function?
Located in carotid and ascending aorta Responsible for all ventilatory response to hypoxia Adapt to increase PAO2
128
What are peripheral chemoreceptors sensitive to?
PaCO2, PaO2 and pH
129
How does CO2 cause you to take a breath?
CO2 crosses blood-brain barrier CO2 combines with water, HH eqtn more acidic H+ conc rises in CSF Urge to take breath
130
How does an increase in PACO2 affect ventilation?
Increases ventilatory response
131
What are the lung receptors?
Stretch J Irritant
132
Where are stretch receptors found and what is their role?
Smooth muscle of conducting airway Sense lung volume and slowly adapt
133
What are J receptors and where are they found?
Juxtapulmonary capillary Vascular based, pulmonary and bronchial C fibres
134
Where are irritant receptors found and what is their role?
Large conducting airways Rapidly adapt, e.g. cough, gasp
135
What are central chemoreceptors sensitive to?
PaCO2
136
What is the dual blood supply in the lung?
Pulmonary from R vent, 100% of blood supply Bronchial, 2% of L vent output
137
Describe pulmonary circulation
100% of CO RBC takes around 5 secs to pass through 280 billion capillaries and 300 million alveoli
138
How big is the surface area for gas exchange?
50-100m^2
139
What are some features of pulmonary arteries?
Thin vessel wall Minor muscularization Blood doesn't need to be redistributed as much
140
What are some features of systemic arteries?
Thick vessel walls as need to maintain high pressure Very muscularized Redistribution of blood needed
141
What is pulmonary arterial pressure?
25/8mmHg
142
What is standard left and right ventricular pressure?
LV: 120/0 RV: 25/0
143
What is Pouiseuille's law?
Resistance = (8 x length x viscosity)/pi x radius^4
144
What is the equation for pressure across a circuit?
Cardiac output x resistance
145
What is the equation for pressure across pulmonary circulation?
mean pulmonary artery pressure - left atrial pressure = CO x pulmonary vaascular resistance
146
How can resistance be reduced in circulation?
Recruit more capillaries by opening more Distend more vessels Stops PA pressure going very high on exercise
147
What are the blood gases for type 1 respiratory failure?
pO2 less than 8kPa pCO2 normal/ less than 6 kPa
148
What are the blood gases for type 2 respiratory failure?
pO2 less than 8kPa pCO2 more than 6 kPa
149
What are the main causes of hypoxaemia?
Hypoventilation Diffusion impairment V/Q mismatch Shunting
150
What is hypoventilation?
Cause of type 2 respiratory failure Failure to ventilate, not enough to O2 in and CO2 out
151
What are some causes of hypoventilation and type 2 respiratory failure?
Muscle weakness (muscular dystrophy, motor neurone disease) Skin problems (burns) Obesity Loss of respiratory drive (opioid drugs)
152
What is a diffusion impairment?
Something interfering with diffusion in lungs Pulmonary oedema affecting gaseous diffusion Interstitial fibrosis affecting membrane diffusion Anaemia impairing oxygen delivery
153
What is V/Q mismatch (ventilation/perfusion)
Rate of perfusion and ventilation not equal
154
What is shunting?
Can be a complete or partial reduction ventilation Blood going through but not involved in gas transfer
155
What is intracardiac shunting?
Eisenmenger's syndrome Hole in septum in heart - Blood flows left to right, more blood going through PA at high pressure, damages them, pressure and resistance increase - RV pressure eventually higher than LV, deoxy blood moves to left atrium - Cyanosis, clubbing, polycythaemia
156
What can cause V/Q mismatch?
Infection Asthma Oedema Pulmonary emboli
157
What is hypoxic pulmonary vasoconstriction?
Reducing blood flow to non oxygenated areas Resolving V/Q mismatch Can cause local or general hypoxia
158
What is a pulmonary embolism?
Clot in the lung, often from DVT Central = ischaemia Peripheral = infarction
159
What is the alveolar gas equation?
PAO2 = PiO2 - PaCO2/ R R = 0.8
160
What is respiratory failure?
Inability to maintain normal blood gases Always signified by low blood oxygen (below 8kPa) If CO2 does go up, it's above 6.5
161
What is hypercapnia?
High PaCO2
162
Examples of acute respiratory failure causes
Opiate overdose Embolism Trauma
163
Examples of chronic respiratory failure causes
COPD Fibrosis
164
Examples of some causes of type 1 respiratory failure
PE COPD Asthma Pulmonary oedema Pulmonary fibrosis
165
Examples of some causes of type 2 respiratory failure
Neuromuscular issues COPD Asthma Laryngeal oedema Sleep apnoea
166
What are some clinical features of hypoxia?
Cyanosis Irritability Reduced intellectual functioning Reduced consciousness Convulsions
167
What are some clinical features of hypercapnia?
Irritability Warm skin Bounding pulse Headache Papillaoedema
168
What is FeNO?
Exhaled nitric oxide Measured in parts per billion Marker of eosinophilic airway inflammation Generally increased in asthma Normal is less than 25ppb, high more than 50ppb
169
What are some common workplace causes of asthma? (high molecular weight allergens)
Grain Wood Latex Flour Animals, fish
170
What are some low molecular weight causes of asthma?
Glutaraldehyde Paint Metals Isocyanates
171
What is asthma?
a common chronic inflammatory disease of the airways characterised by: - variable and recurring symptoms - reversible airflow obstruction and bronchospasm
172
Common symptoms of asthma
Wheezing Coughing Chest tightness Shortness of breath
173
What is hypersensitivity pneumonitis?
An inflammation of the alveoli caused by hypersensitivity to inhaled agents Fibrotic or non-fibrotic Very significant environmental influences
174
What is COPD?
Chronic obstructive pulmonary disease Obstructive lung disease characterised by chronically poor airflow Worsens over time
175
Main symptoms of COPD
Shortness of breath Cough Sputum production
176
How is the smooth muscle in the airways regulated by the autonomic NS?
Contractile signals cause increase in intracellular calcium in smooth muscle Activates actin-myosin contraction
177
How does the parasympathetic NS cause bronchoconstriction?
Vagus nerve neuron terminates in airway wall Short post-synaptic nerve fibres reach muscle and release acetylcholine M3 muscarinic receptors on muscle cells activated Stimulates smooth muscle contraction
178
How do anticholinergic and anti-muscarinic drugs work?
M3 receptor blocked Effects of acetylcholine blocked Parasymp inhibited Bronchodilation
179
What is ipratropium bromide (atrovent)?
Short acting antimuscarinic Inhaled Relaxes airways in asthma and COPD
180
What are LAMAs?
Long acting anti-muscarinics Used in asthma and COPD Reduced exacerbations
181
Examples of inhaled anti-muscarinics
Tiotropium Glycopyrronium Aclidinium Umeclidinium
182
How does the sympathetic nervous system affect the airways?
Release noradrenaline Activates beta-2 adrenergic receptors Muscle relaxation
183
Example of short acting beta 2 agonists
Salbutamol (normally given with steroids in asthma, not alone)
184
Example of long acting beta 2 agonists
Salmeterol Formoterol
185
What are some adverse effects of beta 2 agonists?
Raising cyclic AMP, hypokalaemia Tachycardia Hyperglycaemia
186
What would be used in immediate management of asthma attack?
Oxygen if sats too low Salbutamol nebuliser 5mg Ipratropium neubliser 0.5mg Prednisolone 30-60mg Magnesium/aminophylline (in specialist setting)
187
What is in the humoural part of the immune system?
Immunoglobulins Complement Cytokines
188
Types of antibodies and what they do
IgM: circulating tetramers made at beginning of infection IgG: specific monomers targeting single epitopes IgE: implicated in allergy, to parasitic threats IgA: forms dimers, mucosal tissue, protection of neonatal gut and in breast milk IgD: monomers that induce antibodies and B cells, activates basophils and mast cells
189
What is Type 1 hypersensitivity in the lung?
Mediated by IgE (degranulation of mast cells, histamine predominant mediator) Prostaglandins and leukotrienes can be synthesised and cause secondary effect Anaphylaxis and hayfever Immediate (within an hour)
190
What is type 2 hypersensitivity in the lung?
Mediated by cytotoxic antibodies (IgG or IgM) Hours to days E.g. from transfusions, good pastures
191
What is type 3 hypersensitivity?
Deposition of immune complexes 7-21 days from exposure E.g. hypersensitivity pneumonitis, lupus
192
What is type 4 hypersensitivity?
Mediated by T cells Requires primary sensitization (not first exposure) Takes days to months E.g. TB, Stevens-Johnsons syndrome
193
How would you manage anaphylaxis?
Epipen Adrenaline Steroids Antihistamines
194
What are the genetics for asthma like?
Runs in families Not caused by a single gene mutation Doesn't follow simple mendelian pattern
195
What mutations can cause CF?
Defect in long arm of chromosome 7 coding for CFTR 2000 CF causing CFTR mutations identified Most common mutation is F508del
196
What does an abnormal CFTR protein lead to?
Dysregulated epithelial fluid transport
197
What are class 1-3 genotype classifications for CF?
Class I: no functional CFTR made, G542X Class II: CFTR made but misfolded, F508del Class III: CFTR protein formed into a channel but doesn't open properly, G551D
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What are class 4-6 genotype classifications for CF?
Class IV: CFTR protein formed into a channel but Cl- don't cross properly, R347P Class V: CFTR protein not made in sufficient quantities, A455E Class VI: CFTR with decreased cell surface stability, 120del123
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What is AATD?
Alpha-1 antitrypsin deficiency Autosomal recessive disorder 80 different mutations of SERPINEA1 gene on chromosome 1 M phenotype normal S and Z major disease associations
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What are some consequences of AATD?
Early onset emphysema and bronchiectasis Unopposed action of neutrophil elastase in the lung
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What is 1 atmosphere of pressure equivalent to?
1 bar -1000 millibars 760 mmHg / torr 10 metres of sea water (msw) 33.08 feet of sea water (fsw) 101.3 kilopascals (kPa) 14psi
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What is Boyle's law?
At a constant temperature the absolute pressure of a fixed mass of gas is inversely proportional to its volume P1V1=P2V2
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Describe what happens in apnoea diving (breath hold)
Hyperventilate before Diver descends Gas compresses PaO2, PaN2, PaCO2 rise Eventually CO2 builds up sufficiently to induce desire to breathe Diver returns to surface and PaO2, PaN2, PaCO2 fall
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What is the diving reflex?
Response to cold water can cause: apnoea, bradycardia, peripheral vasoconstriction
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What is apnoea?
where the muscles and soft tissues in the throat relax and collapse sufficiently to cause a total blockage of the airway
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What is Dalton's law?
Total pressure exerted by a mixture of gases is equal to the sum of the pressures that would be exerted by each of the gases if it alone were present and occupied the total volume (sum of all=total pressure of mixture)
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What happens in decompression illness after diving?
Nitrogen compressed into tissues in descent, bubbles trapped in skin and nerves Ascend, bubbles increase in size due to boyle's law Very serious, appears as rash
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What are lorrain smith effect clinical signs?
Cough, chest tightness, chest pain, shortness of breath Straight after diving
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What are the 2 types of decompression illness?
Type 1: cutaneous Type 2: neurologic
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How can you calculate PiGas?
Patm x FiGas
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What is the alveolar gas equation?
PAO2 = PiO2 - PaCO2/ R R assumed to be 0.8
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What is A-aDO2?
Alveolar- arterial O2 difference Normally small difference in partial pressure, at 1kPa
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What is the normal range for PaO2 and PaCO2?
PaO2 = 10.5-13.5 kPa PaCO2 = 4.5-6 kPa
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What is the normal pH range?
7.36-7.44
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What happens to FiO2 and PiO2 as you ascend (e.g. a mountain)?
Fraction stays the same Pressure drops as you get higher
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What is the normal response to elevating (e.g climbing a mountain)?
Hypoxia leads to.. Hyperventilation at 10000ft altitude - Increases minute ventilation - Lowers PaCO2 - Alkalosis initially - Tachycardia
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What happens after prolonged high altitude (e.g. a week)
Alkalosis compensated by renal bicarbonate excretion Adapt to high alt
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What physiological changes occur as you ascend a height?
PiO2 falls, Decreased PAO2 and PaO2 Detected: Peripheral chemoreceptors fire Activates increased ventilation Decreases PaCO2 Increases PAO2 and PaO2
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What is acute mountain sickness?
Recent ascent to over 2500m Lake Louise score greater than or equal to 3 Must have a headache and one other symptom Can only be reliably treated by descent Consequence of reduced ambient pressure
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What are features of high altitude pulmonary oedema?
Unacclimatised individuals Cough, shortness of breath Rapid ascent above 8000ft (2438m) Treatment: descend straight away
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What happens if the volume of the thoracic cavity increases?
Volume in lungs increases Pressure in lungs decrease
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What happens if the volume of the thoracic cavity decreases?
Volume of lungs decrease Pressure in lungs increases
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What is the process of inspiration?
Contraction of diaphragm and external intercostals Increase of volume in thoracic cavity and lungs Pressure in lungs decreases Air moves in down pressure gradient
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What is the process of expiration?
Relaxation of diaphragm and external intercostals Decrease in volume of thoracic cavity and lungs Elastic recoil allows them to return to original size Increase in pressure within lungs Air moves out down pressure gradient
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What muscles are involved in active inspiration (deeper breathing)
Scalenes Sternocleidomastoid Pectoralis major and minor Serratus anterior Latissimus dorsi
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What muscles are involved in active expiration?
Anterolateral abdominal wall Internal intercostal Innermost intercostal
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What does laplaces law state?
The pressure within a cylinder or sphere is proportional to the surface tension divided by the radius
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What makes up the respiratory control centre?
Pons: pneumotaxic and apneustic centres Medulla: dorsal and ventral groups
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What do the pneumotaxic and apneustic centres in pons do?
Control rate and pattern of breathing
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What do the medulla ventral and dorsal groups do?
Ventral controls expiration Dorsal controls inspiration
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What do central chemoreceptors do?
Detect changes in PaCO2 and send impulses to RCC to correct this
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What happens if central chemoreceptors detect an increase in PaCO2?
Increase in ventilation
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What happens if central chemoreceptors detect a decrease in PaCO2?
Decrease in ventilation
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What happens when the peripheral chemoreceptors detect low levels of pO2?
signals sent via CN 9&10 to medulla and pons Resp rate and tidal volume increased Blood flow directed to kidneys and brain as most sensitive to hypoxia Cardiac output increased
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What is resistance like in inspiration?
intrathoracic pressure surrounding the smaller airways is reduced, allowing for airway expansion. As the radius of the airways increases, resistance to airflow is lower during this inspiratory phase
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What is resistance like in expiration?
intrathoracic pressure increases due to the lower volume of the thoracic cavity. pressure leads to narrowing of the smaller airways, so resistance is higher during expiration
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What is radial traction?
elastic fibres of the surrounding alveoli pull on the walls of small airways and hold them open during expiration helps prevent airway collapse
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What secretes surfactant?
Type 2 pneumocytes
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What affects the rate of diffusion?
Membrane surface area Membrane thickness Pressure difference
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How is oxygen transported in the blood?
Dissolved in the blood (1.5%) Bound to haemoglobin (98.5%)
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What is the main role of CO2?
regulate the pH of the blood
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How is CO2 transported in the blood?
Carbamino Compounds Hydrogen Carbonate (HCO3–) Dissolved CO2
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What is gas exchange?
the process by which oxygen and carbon dioxide move between the bloodstream and the lungs
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What is the function of gas exchange?
ensure a constant supply of oxygen to tissues remove carbon dioxide to prevent its accumulation
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What does Henry's law state?
The amount of oxygen that dissolves into the bloodstream is directly proportional to the partial pressure of oxygen in alveolar air
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How does solubility affect gas diffusion ina liquid?
more soluble a gas is, the faster it will diffuse
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What is perfusion?
Total volume of blood reaching the pulmonary capillaries in a given time period
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What is ventilation?
the volume of gas inhaled and exhaled from the lungs in a given time period, usually a minute Tidal volume x resp rate
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What is the normal V/Q ratio?
Ideal would be 1 In humans normally 0.8
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How does gravity affect V/Q?
Pleural pressure is increased at the base of the lungs, resulting in more compliant alveoli and increased ventilation Hydrostatic pressure is decreased at the apex of the lung, resulting in decreased flow and decreased perfusion As perfusion increases with gravity, the apical and middle zones of the lung see the greatest relative increase in their perfusion rate with an increased cardiac output, such as during exercise.
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What are IgM antibodies?
Circulating tetramers made at the beginning of infection
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What are IgG antibodies?
Monomer highly specific antibodies targeting single epitopes
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What are IgE antibodies?
Likely to have developed in response to parasitic threats. Implicated in allergy, particularly alongside eosinophils
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What are IgA antibodies?
Expressed in mucosal tissue. Forms dimers. Protects the neonatal gut (expressed in breast milk)
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What does IgD do?
Monomers, induction of antibodies in B cells, activates basophils and mast cells
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What is the predominant mediator of type 1 sensitivity?
Histamine
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What mediates type 4 sensitivity?
T-cell
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When is haemoglobin in the Relaxed (R) State?
When oxygen first binds Alters shape Higher affinity for oxygen
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When is haemoglobin in the Tense (T) State?
When no oxygen is bound Low affinity for oxygen
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What causes the oxygen dissociation curve to shift to the left?
increase in oxygen affinity
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What causes the oxygen dissociation curve to shift to the right?
decrease in oxygen affinity
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What is cooperativity in oxygen binding to haemoglobin?
As the number of oxygen molecules bound to haemoglobin increases, the affinity of haemoglobin for oxygen increases
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What causes the oxygen dissociation curve to shift to the right?
Low pH Increase in temperature Increase in PCO2 Increase in 2,3 DPG All cause lower affinity for oxygen
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What causes the oxygen dissociation curve to shift to the left?
High pH Decrease in temperature Decrease in PCO2 Decrease in 2,3 DPG HbF not HbA All increase affinity for oxygen