Respiratory Flashcards
What makes up the upper respiratory tract?
Nasal cavity
Pharynx
Larynx
What makes up the lower respiratory tract?
Trachea
Primary bronchi
Lungs
What are the main functions of the nose in the respiratory tract?
Filtration
Defence- cilia take inspired particulates back to be swallowed
Warms and humidifes air
Describe the anatomy of the nose
Anterior nares open into enlarged vestibule which is lined with skin and stiff hairs
Turbinates double surface area
What are the 3 turbinates of the nose?
Superior meatus
Middle meatus
Inferior meatus
What are the 4 types of paranasal sinuses?
Frontal
Maxillary
Ethmoid
Sphenoid
They are pneumatised areas of these bones
They are evaginations of mucous membranes form the nasal cavity
Describe anatomy (location) of frontal sinuses
Within frontal bone
Midline septum
Over orbit and across superciliary arch
Supplied by ophthalmic division of nerve V
Describe anatomy (location) of maxillary sinuses
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
Describe anatomy (location) of ethmoid sinuses
Between the eyes
Labyrinth of air cells (looks like honeycomb)
Drain into middle meatus by semilunar hiatus
Supplied by ophthalmic and maxillary nerve V
Describe anatomy (location) of sphenoid sinuses
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
What is the pharynx?
Fibromuscular tube lined with epithelium
Connects back of nose to larnyx
What is at the nasopharynx?
Eustachian tube enters into nasopharynx
Inferiorly at soft palate enters to oropharynx
Pharyngeal tonsils on posterior wall
Describe anatomy of oropharynx
Back of mouth, soft palate anterior to oro
Palatine tonsils on lateral walls
Inferior to hyoid bone
Palatoglossal folds
Palatopharyngeal folds
Describe the larynx (anatomy and function)
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
What are the single laryngeal cartilages?
Epiglottis
Thyroid
Cricoid
What are the double laryngeal cartilages?
Cuneiform
Corniculate
Arytenoid
Which nerves innervate larynx?
Vagus (CNX) splits into superior laryngeal nerve and recurrent laryngeal nerve
What is the role of the superior laryngeal nerve?
Provides sensation to larynx (internal) and supplies cricothyroid muscle (external)
What is the role of the recurrent laryngeal nerve?
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
What is a normal/average minute ventilation?
approx 5 litres
What is normal CO amount?
approx 5 litres
What is the size of the gas exchange surface of each lung (spread out)
20m^2
What are the main airways (biggest to smallest) in the lower resp tract?
Trachea
Main bronchi
Lobar bronchi
Segmental branches
Respiratory bronchiole
Terminal bronchiole
Alveolar ducts and branches
What is the structure of the trachea?
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
What is the basic structure of the R main bronchus?
1cm-2.5cm long
Vertically disposed, shorter than L
What is the basic structure of the L main bronchus?
5cm long
Longer than R
What is the acinus?
Functional unit distal to the terminal bronchiole
What are the 2 layers of pleura?
Visceral: applied to lung surface, only autonomic innervation
Parietal: applied to internal chest wall, pain sensation
Describe the pleura
Visceral and parietal
Each a single cell layer
Continuous with each other at lung root
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
Examples of inflammation-mediated tissue damage in lung
COPD
Acute respiratory distress syndrome
Bronchiectasis
Asthma
Interstitial lung disease
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)
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
What cells can amplify acute inflammation?
Specialist macrophages:
- Kupffer cells (liver)
- Histiocytes (skin and bone)
- Dendritic cells
- Alveolar macrophages (lung)
What recognises pathogens we haven’t seen before?
Pattern recognition receptors
Types of signalling receptors for pattern recognition
Toll-like receptors
Nod-like receptors
Types of endocytic receptors
Mannose
Glucan
Scavenger
What are TLRs?
Toll-like receptors
Recognise conserved molecular patterns in pathogens
Also recognise endogenous mediators of inflammation
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
What is macrophage plasticity?
Macrophages can change behaviour to suit environment
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
What do primary neutrophil granules contain?
Myeloperoxidase
Elastase
Cathespins
Defensins
What do secondary neutrophil granules contain?
Receptors
Collagenase
Lysozyme
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)
Life of a neutrophil from threat to death
Identify threat
Activation
Adhesion
Migration
Phagocytosis
Bacterial killing
Apoptosis
What do neutrophil receptors recognise?
Bacterial structures- cell wall, lipids, peptides
Host mediators- cytokines, complement cascade, lipids
Host opsonins- FcR, CR3
Host adhesion molecules
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
How does neutrophil adhesion work?
Margination from selectins, rolling
Integrins mediate firm adhesion
Require changes in endothelium and neutrophils
Neutrophils flatten out and migrate
What can CD18 deficiency cause?
No transendothelial migration
Delayed separation of umbilical cord
Recurrent severe cutaneous and deep infections
What happens in phagocytosis?
Phagocytic cup extended and fuses around bacteria
Forms phagosome
Fusion with granules forms phagolysome
What is generated in bacterial killing?
Reactive oxygen species generated by NADPH oxidase and ATP
What is intrinsic defence?
Always present
Physical and chemical
Apoptosis
Autophagy
Present anti-viral proteins
What is innate defence?
Induced by infection
Interferon
Cytokines
Macrophages
NK cells
What is adaptive immunity?
Tailored to a pathogen
T and B cells
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
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.
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
What are the chemical epithelial barriers?
Anti-proteinase
Anti-fungal peptides
Anti-microbial peptides
Antiviral proteins
Opsins
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)
What is the role of mucus in defence?
Protects the epithelium from foreign material and fluid loss
What is the reason for coughing and sneezing?
Non-immune defence mechanisms
What is a cough?
Expulsive reflex that protects the lungs and respiratory passages from foreign bodies
What can cause a cough?
Irritants: fumes, dust
Diseased conditions: COPD, tumours
Infections
Which nerves can be involved in triggering a cough?
Afferent nerves: trigeminal, glossopharnygeal, superior laryngeal and vagus
Efferent nerves: laryngeal and spinal
What is a sneeze?
Involuntary expulsion of air containing irritants from the nose
What can cause a sneeze?
Irritation of nasal mucosa
Excess fluid in airway
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
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
What goes wrong in obstructive lung disease?
Obstruction in airway
Production of respiratory secretions and pathogenic material that can’t be cleared through escalator
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
What are the muscles involved in inspiration?
External intercostals
Diaphragm, C3,4,5
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
How much dead space is in the lung?
Anatomic deadspace: 150mls
Alveolar deadspace: 25mls
Physiological is total so 175mls
What is the pressure of pulmonary circulation?
24mmHg/10mmHg
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
What does alveolar perfusion depend on?
Pulmonary artery pressure
Pulmonary venous pressure
Alveolar pressure
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
What does PaCO2 mean?
Partial pressure of CO2 in artery
What does PACO2 mean?
Partial pressure of CO2 in alveolar
What does PaO2 mean?
Partial pressure of O2 in artery
What does PAO2 mean?
Partial pressure of O2 in alevolus
What does PiO2 mean? And what does it equal?
Pressure of inspired oxygen
21kPa at sea level
What does FiO2 mean? And what is it?
Fraction of inspired oxygen
0.21
What does V̇A mean?
Rate of alveolar ventilation
What does V̇CO2 mean?
Rate of CO2 production
What is the equation for PaCO2?
PaCO2 = kV̇CO2 divided by V̇A
normally = 4-6kPa
How is CO2 carried?
Bound to haemoglobin
Dissolved in plasma
As carbonic acid
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
What is the alveolar gas equation?
PAO2 = PiO2 - PaCO2 / R
R = respiratory quotient, 0.8
What are some causes of hypoxia?
Alveolar hypoventilation
Reduced PiO2
Ventilation/perfusion mismatching
Diffusion abnormality
What is the normal pH of arterial blood?
pH = 7.40 (.36-.44)
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)
Equation for carbonic acid equilibrium
CO2 + H2O <—–> H2CO3 <—–> H+ + HCO3-
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
What is the henderson hasselbach eqtn for acid/base control?
pH = 6.1 + log10 ( [HCO3-] / [0.03 x PCO2] )
What is respiratory acidosis?
increased PaCO2, decreased pH, mild increased HCO3-
What is respiratory alkalosis?
decreased PaCO2, increased pH, mild decreased HCO3-
What is metabolic acidosis?
reduced bicarbonate and decreased pH
What is metabolic alkalosis?
increased bicarbonate and increased pH
What is tidal volume?
The volume of air entering or leaving the lungs during a single breath
Usually 0.5L resting
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
What is inspiratory capacity?
Max volume of air that can be inspired at the end of a normal quiet expiration
IRV + TV
3 Litres
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
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
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
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
What is total lung capacity?
Max volume of air that the lungs can hold
Sum of all
Average value = 5700mL- 6L
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
What is peak expiratory flow?
Single measure of highest flow during expiration
Measured via peak flow meter
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
Different ways to measure lung function/ volume
Total body plethysmography
Peak flow
Gas dilution
Spirometry
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
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
What is an abnormal value of FVC and what does that suggest?
Below 80%
Sign of airway restriction
What ratio suggests airway obstruction?
Ratio between FEV1 and FVC is less than 70%
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
What are FEV1 and FVC like in asthma?
Normal
FEV1 sometimes reduced
What are the typical blood gases like for asthma?
Abnormalities in acute asthma attacks, otherwise normal
Drop in PaCO2
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
What are the FEV1 and FVC like in COPD?
FEV1 reduced significantly
FVC normal or reduced
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
Where are the major locations for phasic discharge for breathing?
Pons: pneumotaxic and apneustic
Medulla: dorsal respiratory group (predominantly inspiration) and ventral respiratory group
What is the central pattern generator?
Located within dorsal and ventral RG
Neural network that starts, stops and resets integrator of background ventilatory drive
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
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
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
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
What are peripheral chemoreceptors sensitive to?
PaCO2, PaO2 and pH
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
How does an increase in PACO2 affect ventilation?
Increases ventilatory response
What are the lung receptors?
Stretch
J
Irritant
Where are stretch receptors found and what is their role?
Smooth muscle of conducting airway
Sense lung volume and slowly adapt
What are J receptors and where are they found?
Juxtapulmonary capillary
Vascular based, pulmonary and bronchial C fibres
Where are irritant receptors found and what is their role?
Large conducting airways
Rapidly adapt, e.g. cough, gasp
What are central chemoreceptors sensitive to?
PaCO2
What is the dual blood supply in the lung?
Pulmonary from R vent, 100% of blood supply
Bronchial, 2% of L vent output
Describe pulmonary circulation
100% of CO
RBC takes around 5 secs to pass through
280 billion capillaries and 300 million alveoli
How big is the surface area for gas exchange?
50-100m^2
What are some features of pulmonary arteries?
Thin vessel wall
Minor muscularization
Blood doesn’t need to be redistributed as much
What are some features of systemic arteries?
Thick vessel walls as need to maintain high pressure
Very muscularized
Redistribution of blood needed
What is pulmonary arterial pressure?
25/8mmHg
What is standard left and right ventricular pressure?
LV: 120/0
RV: 25/0
What is Pouiseuille’s law?
Resistance = (8 x length x viscosity)/pi x radius^4
What is the equation for pressure across a circuit?
Cardiac output x resistance
What is the equation for pressure across pulmonary circulation?
mean pulmonary artery pressure - left atrial pressure = CO x pulmonary vaascular resistance
How can resistance be reduced in circulation?
Recruit more capillaries by opening more
Distend more vessels
Stops PA pressure going very high on exercise
What are the blood gases for type 1 respiratory failure?
pO2 less than 8kPa
pCO2 normal/ less than 6 kPa
What are the blood gases for type 2 respiratory failure?
pO2 less than 8kPa
pCO2 more than 6 kPa
What are the main causes of hypoxaemia?
Hypoventilation
Diffusion impairment
V/Q mismatch
Shunting
What is hypoventilation?
Cause of type 2 respiratory failure
Failure to ventilate, not enough to O2 in and CO2 out
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)
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
What is V/Q mismatch (ventilation/perfusion)
Rate of perfusion and ventilation not equal
What is shunting?
Can be a complete or partial reduction ventilation
Blood going through but not involved in gas transfer
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
What can cause V/Q mismatch?
Infection
Asthma
Oedema
Pulmonary emboli
What is hypoxic pulmonary vasoconstriction?
Reducing blood flow to non oxygenated areas
Resolving V/Q mismatch
Can cause local or general hypoxia
What is a pulmonary embolism?
Clot in the lung, often from DVT
Central = ischaemia
Peripheral = infarction
What is the alveolar gas equation?
PAO2 = PiO2 - PaCO2/ R
R = 0.8
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
What is hypercapnia?
High PaCO2
Examples of acute respiratory failure causes
Opiate overdose
Embolism
Trauma
Examples of chronic respiratory failure causes
COPD
Fibrosis
Examples of some causes of type 1 respiratory failure
PE
COPD
Asthma
Pulmonary oedema
Pulmonary fibrosis
Examples of some causes of type 2 respiratory failure
Neuromuscular issues
COPD
Asthma
Laryngeal oedema
Sleep apnoea
What are some clinical features of hypoxia?
Cyanosis
Irritability
Reduced intellectual functioning
Reduced consciousness
Convulsions
What are some clinical features of hypercapnia?
Irritability
Warm skin
Bounding pulse
Headache
Papillaoedema
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
What are some common workplace causes of asthma? (high molecular weight allergens)
Grain
Wood
Latex
Flour
Animals, fish
What are some low molecular weight causes of asthma?
Glutaraldehyde
Paint
Metals
Isocyanates
What is asthma?
a common chronic inflammatory disease of the airways characterised by:
- variable and recurring symptoms
- reversible airflow obstruction and bronchospasm
Common symptoms of asthma
Wheezing
Coughing
Chest tightness
Shortness of breath
What is hypersensitivity pneumonitis?
An inflammation of the alveoli caused by hypersensitivity to inhaled agents
Fibrotic or non-fibrotic
Very significant environmental influences
What is COPD?
Chronic obstructive pulmonary disease
Obstructive lung disease characterised by chronically poor airflow
Worsens over time
Main symptoms of COPD
Shortness of breath
Cough
Sputum production
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
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
How do anticholinergic and anti-muscarinic drugs work?
M3 receptor blocked
Effects of acetylcholine blocked
Parasymp inhibited
Bronchodilation
What is ipratropium bromide (atrovent)?
Short acting antimuscarinic
Inhaled
Relaxes airways in asthma and COPD
What are LAMAs?
Long acting anti-muscarinics
Used in asthma and COPD
Reduced exacerbations
Examples of inhaled anti-muscarinics
Tiotropium
Glycopyrronium
Aclidinium
Umeclidinium
How does the sympathetic nervous system affect the airways?
Release noradrenaline
Activates beta-2 adrenergic receptors
Muscle relaxation
Example of short acting beta 2 agonists
Salbutamol
(normally given with steroids in asthma, not alone)
Example of long acting beta 2 agonists
Salmeterol
Formoterol
What are some adverse effects of beta 2 agonists?
Raising cyclic AMP, hypokalaemia
Tachycardia
Hyperglycaemia
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)
What is in the humoural part of the immune system?
Immunoglobulins
Complement
Cytokines
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
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)
What is type 2 hypersensitivity in the lung?
Mediated by cytotoxic antibodies (IgG or IgM)
Hours to days
E.g. from transfusions, good pastures
What is type 3 hypersensitivity?
Deposition of immune complexes
7-21 days from exposure
E.g. hypersensitivity pneumonitis, lupus
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
How would you manage anaphylaxis?
Epipen
Adrenaline
Steroids
Antihistamines
What are the genetics for asthma like?
Runs in families
Not caused by a single gene mutation
Doesn’t follow simple mendelian pattern
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
What does an abnormal CFTR protein lead to?
Dysregulated epithelial fluid transport
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
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
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
What are some consequences of AATD?
Early onset emphysema and bronchiectasis
Unopposed action of neutrophil elastase in the lung
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
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
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
What is the diving reflex?
Response to cold water can cause: apnoea, bradycardia, peripheral vasoconstriction
What is apnoea?
where the muscles and soft tissues in the throat relax and collapse sufficiently to cause a total blockage of the airway
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)
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
What are lorrain smith effect clinical signs?
Cough, chest tightness, chest pain, shortness
of breath
Straight after diving
What are the 2 types of decompression illness?
Type 1: cutaneous
Type 2: neurologic
How can you calculate PiGas?
Patm x FiGas
What is the alveolar gas equation?
PAO2 = PiO2 - PaCO2/ R
R assumed to be 0.8
What is A-aDO2?
Alveolar- arterial O2 difference
Normally small difference in partial pressure, at 1kPa
What is the normal range for PaO2 and PaCO2?
PaO2 = 10.5-13.5 kPa
PaCO2 = 4.5-6 kPa
What is the normal pH range?
7.36-7.44
What happens to FiO2 and PiO2 as you ascend (e.g. a mountain)?
Fraction stays the same
Pressure drops as you get higher
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
What happens after prolonged high altitude (e.g. a week)
Alkalosis compensated by renal bicarbonate excretion
Adapt to high alt
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
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
What are features of high altitude pulmonary oedema?
Unacclimatised individuals
Cough, shortness of breath
Rapid ascent above 8000ft (2438m)
Treatment: descend straight away
What happens if the volume of the thoracic cavity increases?
Volume in lungs increases
Pressure in lungs decrease
What happens if the volume of the thoracic cavity decreases?
Volume of lungs decrease
Pressure in lungs increases
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
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
What muscles are involved in active inspiration (deeper breathing)
Scalenes
Sternocleidomastoid
Pectoralis major and minor
Serratus anterior
Latissimus dorsi
What muscles are involved in active expiration?
Anterolateral abdominal wall
Internal intercostal
Innermost intercostal
What does laplaces law state?
The pressure within a cylinder or sphere is proportional to the surface tension divided by the radius
What makes up the respiratory control centre?
Pons: pneumotaxic and apneustic centres
Medulla: dorsal and ventral groups
What do the pneumotaxic and apneustic centres in pons do?
Control rate and pattern of breathing
What do the medulla ventral and dorsal groups do?
Ventral controls expiration
Dorsal controls inspiration
What do central chemoreceptors do?
Detect changes in PaCO2 and send impulses to RCC to correct this
What happens if central chemoreceptors detect an increase in PaCO2?
Increase in ventilation
What happens if central chemoreceptors detect a decrease in PaCO2?
Decrease in ventilation
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
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
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
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
What secretes surfactant?
Type 2 pneumocytes
What affects the rate of diffusion?
Membrane surface area
Membrane thickness
Pressure difference
How is oxygen transported in the blood?
Dissolved in the blood (1.5%)
Bound to haemoglobin (98.5%)
What is the main role of CO2?
regulate the pH of the blood
How is CO2 transported in the blood?
Carbamino Compounds
Hydrogen Carbonate (HCO3–)
Dissolved CO2
What is gas exchange?
the process by which oxygen and carbon dioxide move between the bloodstream and the lungs
What is the function of gas exchange?
ensure a constant supply of oxygen to tissues
remove carbon dioxide to prevent its accumulation
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
How does solubility affect gas diffusion ina liquid?
more soluble a gas is, the faster it will diffuse
What is perfusion?
Total volume of blood reaching the pulmonary capillaries in a given time period
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
What is the normal V/Q ratio?
Ideal would be 1
In humans normally 0.8
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.
What are IgM antibodies?
Circulating tetramers made at the beginning of infection
What are IgG antibodies?
Monomer highly specific antibodies targeting single epitopes
What are IgE antibodies?
Likely to have developed in response to parasitic threats. Implicated in allergy, particularly alongside eosinophils
What are IgA antibodies?
Expressed in mucosal tissue.
Forms dimers.
Protects the neonatal gut (expressed in breast milk)
What does IgD do?
Monomers, induction of antibodies in B cells, activates basophils and mast cells
What is the predominant mediator of type 1 sensitivity?
Histamine
What mediates type 4 sensitivity?
T-cell
When is haemoglobin in the Relaxed (R) State?
When oxygen first binds
Alters shape
Higher affinity for oxygen
When is haemoglobin in the Tense (T) State?
When no oxygen is bound
Low affinity for oxygen
What causes the oxygen dissociation curve to shift to the left?
increase in oxygen affinity
What causes the oxygen dissociation curve to shift to the right?
decrease in oxygen affinity
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
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
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
