Respiratory Flashcards
(148 cards)
1
Q
What are the functions of the nose?
A
Warm inspired air
increase humidity of the air
filter function
defence (cilia take inhaled particles backwards to be swallowed)
2
Q
What are turbinates?
A
Structures inside of the nose that increase the surface area of the nasal cavity. They are an outpouching of bone lined with epithelium.
*Superior meatus:
Olfactory epithelium
Cribriform plate
Sphenoid sinus
- Middle meatus
Sinus openings - Inferior meatus
nasolacrimal duct
3
Q
Describe the paranasal sinuses
A
We have four pairs of sinuses:
Frontal
Maxillary
Ethmoid
Sphenoid bones
They are arranged in pairs.
Evagination of the mucous membrane from the nasal cavity.
4
Q
Describe the frontal sinuses
A
Within the frontal bones
They have a midline septum that is not in the actual midline of the body.
They go over the orbit and across the superciliary arch (where most people’s eyebrows are).
They are supplied by the opthalmic division of the V cranial nerve. The trigeminal nerve innervates sensory components of the sinus.
5
Q
Describe the maxillary sinuses
A
Located within the body of the maxilla
They have a pyramidal shape:
* Base of the pyramid is the lateral wall of the nose
* Apex is the zygomatic process of the maxilla.
* Roof - floor of the orbit.
* Floor - alveolar process
The maxillary sinus opens into the middle meatus through the hiatus semilunaris. This allows the fluid in the sinus to drain back into the nasal cavity.
6
Q
Describe the ethmoid sinuses
A
Located between the eyes.
Composed of a labyrinth of air cells.
They drain into by the semilunar hiatus into the middle meatus.
Nerve supply - opthalmic and maxillary divisions of V cranial nerve.
7
Q
Describe the sphenoid sinuses
A
It is a small sinus that
It is inferior to the optic canal, dura and pituitary gland.
Empties into the sphenoethmoidal recess, lateral to the attachment of the nasal septum.
Innervated by the opthalmic V.
It is close to the carotid artery, the III, IV, V and VI cranial nerves.
Medial to the cavernous sinus.
8
Q
What is the phraynx?
A
Links the back of the nose to the larynx.
9
Q
What is the larynx?
A
It is a very complicated valve.
Prevents liquids and food from entering the lung.
Has a rigid structure - comprised of cartilage. Multiple muscles involved.
The arytenoid cartilages rotate on the cricoid cartilage to change the vocal cords.
The cartilages in the larynx are the following:
*Single:
Epiglottis x1
Thyroid x1
Cricoid x1
*double:
Cuneiform x2
Corniculate x2
Arytenoid x2
10
Q
How is the larynx innervated?
A
Innervated by the 2 branches of the vagus (X) nerve:
*Superior laryngeal nerve. The internal branch is sensory.
The external branch supplies the cricothyroid muscle.
*Recurrent laryngeal nerve innervates all muscles bar the cricothyroid. The L and R recurrent laryngeal nerves are different.
11
Q
How are the lungs arranged in the thoracic cavity?
A
ML can’t be seen poseriorly.
12
Q
What are the differences between the right and left main bronchi?
A
The carina is the point at which the split occurs.
The right main bronchus is more vertical and shorter. (1-2.5cm long).
The L main bronchus is longer and more curved as it must avoid the heart and the aortic arch (5cm long).
13
Q
What is the lower respiratory airway structure?
A
The main airways are as follows:
Trachea.
main bronchi.
lobar bronchi.
segmental bronchi.
respiratory bronchi.
terminal bronchiole.
alveolar ducts and alveoli.
14
Q
What are the branches in the segmental bronchi?
(dont really need to know lol)
A
In the right lung:
Upper lobe - apical, anterior and posterior
Middle lobe - medial and lateral
Lower lobe - apical, anterior, posterior, medial, lateral
In the left lung:
Upper love - apico-posterior, anterior
Lingu
15
Q
How does the structure of the lung tubes change?
A
They slowly become more adapted for gas exchange.
16
Q
What is the acinus?
A
It is a functional unit running out from the terminal bronchiole. The system that starts at the respiratory bronchiole and terminates at the alveoli is called an acinus, and it is functionally characterized by having the ability to both conduct air as well as enable gas exchange.
17
Q
What are the pleura?
A
2 layers of mesodermal origin, each a single cell layer, that are continuous with each other.
Visceral - applied to lung surface. Has only autonomic innervation.
parietal - applied to internal chest wall. Has pain sensation.
fluid between
18
Q
How does the neutrophil help with host defence in the lung?
A
It is part of the innate immune system.
They have multiple functions:
1. Receptors identify the threats. They recognise bacterial structures like cell walls, lipids, peptides. Also host mediators (cytokines, lipids) and other host molecules.
- Activation.
- Adhesion.
- Migration/ chemotaxis. They can quickly identify the site where the threat is, and efficiently deal with it.
- Phagocytosis.
- Bacterial killing
- Apoptosis (programmed cell death).
19
Q
What is inflammation?
A
Vasodilation leading to exudation of plasma, including antibodies.
It causes the activation of biochemical cascades.
It encourages the migration of blood leukocytes into the tissues - mainly neutrophils but also some monocytes.
20
Q
How can inflammation be bad?
A
Repeated inflammation can lead to the death of alveolar cells, through various mechanisms.
21
Q
What is ARDS?
A
Acute respiratory distress syndrome.
A buildup of fluid, immune cells, and other stuff in the alveoli in the lungs.
Also causes thickening of the alveolar walls.
22
Q
How is inflammation initiated?
A
Initiated by epithelial production of hydrogen peroxide, which damages and releases cellular contents.
This stimulates other cells to create cytokines and chemokines, which recruit inflammatory cells causing a cascade in inflammation.
It is amplified by specialist tissue resident macrophages.
These include alveolar macrophages (lung), Kupffer cells (liver), histiocytes (skin and bone) and dendritic cells.
These deal with low level threats and coordinate signalling.
They respond to:
* PAMPs (pathogen associated molecular patterns)
* DAMPs (damage associated molecular patterns).
23
Q
What are the patterns on pathogens?
A
Signalling receptors:
Toll-like receptors (TLRs)
Nod-like receptors (NLRs)
Endocytic receptors (phagocytic receptors):
Mannose receptors
Glucan receptors
Scavenger cells
24
Q
What are the alveolar macrophages?
A
They colonise the lung during foetal development.
Macrophage plasticity:
Macrophages can change their behaviour (phenotype) depending on their environment.
They adapt to the individual threat.
They can also heal surrounding tissues once the threat is gone.
25
Describe neutrophil structure.
They contain granules:
Primary granules contain myeloperoxidase, elactase, cathepsins, defensins. These can damage cells but help in killing baceria.
Secondary granules contain new receptors for the cell surface and other enzymes useful for killing bacteria (lysozymes, collagenase).
Some neutrophils are adhered to the endothelium, but most travel in circulation.
26
How are neutrophils removed?
They take up bacteria and digest them.
They release chemicals that damage tissues. They must be removed, so they undergo apoptosis.
The key effector proteins are cut up by proteases within the cell. The cell is recognised as being apoptotic, so it can be taken up by macrophages.
27
Describe (2) neutrophil activation?
Called stimulus response coupling.
The amount of neutrophils produced must be appropriate to the size of the threat.
This is done by pathways involving calcium, phospholipases, protein kinases and G proteins.
28
Describe (3) neutrophil adhesion
They initially are flowing in the blood.
In the blood, they will be 'captured' by an activated piece of endothelium through a process between selectin molecules on the endothelium and neutrophil. This causes the neutrophil to roll across the endothelium.
They then interact with integrins, which capture the neutrophils fully, causing them to go stationary. They then squeeze between endothelial cells, out of the blood vessels.
29
How to neutrophils do phagocytosis (5)?
Membrane pinching creates a phagosome, inside of which is the pathogen. They then undergo a war.
30
How do neutrophils kill bacteria? (7)
Happens within the phagosome.
The pathogen is killed by enzyme release.
ROS (reactive oxygen species) is generated by NADPH oxidase complex.
31
What is Pouiseuille's law?
Determining flow through a tube
32
How do we determine pressure across circulation?
Principles of V=IR
Pressure across circuit = CO x resistance
Pressure across pulmonary circulation:
mPAP - PAWP = CO x PVR
mPAP - mean pulmonary arterial pressure
PAWP - pulmonary arterial wedge pressure, which is left atrial pressure
CO - cardiac output
PVR - pulmonary vascular resistance.
33
How does the pulmonary arterial pressure stay constant during exercise?
mPAP is stable
CO significantly increases.
Resistance must fall to accommodate this.
This is done by recruiting more capillaries and using them.
Capillary vessels can also be distended.
34
What are the two main causes of hypoxaemia?
Type I and type II respiratory failure.
Both involve a pO2 < 8kPA.
Type I:
pCO2 < 6kPA (normal levels)
Type II:
pCO2 > 6 kPA (abnormally high level)
These are caused, generally, by 4 main things:
* Hypoventilation
* Diffusion impairment
* shunting
* V/Q mismatch
35
How does hypoventilation cause hypoxaemia?
Causes type II respiratory failure. Means alveoli cannot be ventilated properly.
Can be caused by problems with skin, muscular weakness, bones.
Can also be caused by things that control the breathing - drugs that reduce the respiratory drive.
36
How can diffusion impairment cause respiratory failure?
gaseous diffusion:
- Alveoli may be filled with fluid (pulmonary oedema).
Membrane diffusion:
- Interstitial fibrosis
Blood diffusion:
- If you are anaemic, less oxygen can get round the body.
37
What is VQ mismatch, and how does it cause hypoxaemia?
V/Q mismatch
V= ventilation
Q = perfusion.
If the blood flow and air flow are not matched properly, not enough oxygen may be transferred.
If the V/Q ratio is too high/ too low, exchange is ineffecient.
38
What is shunting?
Blood flows into the lungs but no gas exchange occurs.
For example:
- Complete lobar collapse.
Eisenmenger's syndrome causes blood to flow into the RV from LV as pressure in LV is higher. This damages the small pulmonary arteries, remodelling the vessels. They respond by becoming narrower, increasing resistance and pressure. This build in pressure can lead RV pressure to be higher than LV pressure. Deoxygenated blood then flows into the LV, and into systemic circulation. Oxygen saturation is lower.
39
What are the host defences in the lungs?
Intrinsic: always present
Physical and chemical defences: apoptosis, autopahgy, RNA silencing, antiviral proteins.
Innate defence: induced by infection
Macrophages, NK cells, cytokines
Adaptive immunity: tailored to a pathogen
T cells and B cells.
40
What is the function of mucus?
It is a viscoelastic gel containing water, carbohydrates, proteins and lipids.
Secreted by goblet cells and the submucosal glands.
Protects the epithelium from foreign material and from fluid loss.
Mucociliary clearance (rhythmic beating of cilia) and air flow moves mucus from the lower respiratory tract into the pharynx.
41
What is a cough?
An expulsive reflex (voluntary or involuntary) that protects the lungs and respiratory passages from foreign bodies.
Causes:
- Irritants (smoke, fumes, dusts)
- Diseased conditions (COPD, tumours)
- Infections (influenza)
Motor and sensory innervation causes the cough reflex.
42
What is a sneeze?
Involuntary expulsion of air containing irritants from the nose.
Causes:
- Irritation of nasal mucosa.
- Excess fluid in airway
Receptors in the upper respiratory tract detect particulates in the nose. Sensory neurones register this. CNS. Motor neurones - sneeze. Irritant is expelled.
43
What molecules are secrete
- Antiproteases (pathogens may use proteases to invade the epithelium).
- Anti-fungal proteins
- Anti-microbial proteins (focus bacterial pathogens).
- Antiviral proteins
- Opsins are involved in completement pathways.
These are produced by different epithelial cells. Different classes of cells produce many types of chemicals and proteins.
44
How does the airway exhibit functional plasticity?
The respiratory epithelium can essentially complete a complete repair. The basal cell is the fundamental cell, from which other cells differentiate.
Metaplasia is where there is a reversible differentiation from one cell type to another. Some of the epithelium in smokers can be removed and replaced.
45
Why are ventilation as perfusion important for gas exchange?
Ventilation - maintaining conc gradient for diffusion of gases in the air.
perfusion - maintaining conc gradient for diffusion of gases in the blood.
Ventilation and prefusion must be matched to ensure efficient exchange.
46
What is alveolar dead space?
It is the volume of air not contributing to ventilation.
For two reasons:
1) not all inspired air reaches alveoli
2) not all alveoli are perfused with blood.
47
What is typical blood pressure?
Systemic: less than 120/80 mmHg
Pulmonary: 24/10 mmHg
48
What is unique about the arteries in the lungs?
The broncho-vascular artery runs parallel with an airway, not a vein (as is typical).
49
How efficient is gas exchange?
25% through the alveolar capillaries, haemoglobin is fully saturated.
Alveolar perfusion also depends on pulmonary arterial and venous pressure, as well as alveolar pressure.
50
What is the alveolar gas equation?
R = respiratory quotient (ratio of CO2 vol released / vol O2 absorbed. Assume standard = 0.8)
PAO2 = alveolar partial pressure of O2 (same with CO2).
PaO2 = arterial partial pressure of O2 (same with CO2). Can be measured in both CO2 (by pH) and O2 (by HCO3-).
PiO2 = pressure of inspired oxygen
FiO2 = fraction of inspired oxygen
VA = alveolar ventilation
VCO2 = CO2 production.
CO2 elimination:
PaCO2 = kVCO2 / VA
normally PaCO2 = 4-6 kPa.
PAO2= PiO2 - (PaCO2 / R)
51
What are some causes of high CO2?
(high PaCO2)
PaCO2 = kVCO2 / VA
CO2 is carried in the blood in 3 ways:
1. bound to haemoglobin.
2. Plasma dissolved.
3. As carbonic acid.
- VA reduced; reduced minute ventilation.
- VA reduced; increased dead space ventilation by rapid shallow breathing.
- VA reduced; increased dead space by ventilation/ perfusion (V/Q) mismatching.
- High CO2 production.
52
How is blood acidity managed?
Maintaining pH of the blood.
It can change CO2 under predominant respiratory control (rapid change).
It can change HCO3- under predominant renal control (slower change).
In order to keep pH at 7.4, the log ratio in the HH eqution must equal 1.3.
If PaCO2 rises (due to resp failure), HCO3- must rise to compensate (done by the renal compensatory mechanism).
53
What are the four main acid-base disorders?
Respiratory acidosis: increased PaCO2, decreased pH, mild increased HCO3- (where CO2 retention leads to increased carbonic acid dissociation). To compensate, there is increased renal H+ excretion and bicarbonate retention.
Respiratory alkalosis: decreased PaCO2, increased pH, mild decreased HCO3- (CO2 depletion due to hyperventilation). Increases renal bicarbonate loss.
Metabolic acidosis: reduced bicarbonate and decreased pH. Body compensates by hyperventilation to increase CO2 excretion.
Metabolic alkalosis: increased bicarbonate and increased pH (many causes, like alkali ingestion or GI acid loss (ie by vomitting)). Body compensates by hypoventilation and renal bicarbonate excretion.
54
What are some measurements in lung physiology?
TV (tidal volume): vol inhaled and exhaled during a normal breath.
TLC: total lung capacity (typically 5.9L)
VC (vital capacity): vol of lungs after max air exhaled foracbly - small vol remains to prevent lung collapse).
Residual volume (RV): alveolar dead space, ~1.2L.
ERV (expiratory reserve): the vol of air that can be exhaled after a normal tidal expiration ~1.2L.
Inspirational Capacity (IV): the vol that can be inhaled after a normal tidal expiration ~3.5L.
FRC: functional residual capacity: total vol of air in lungs after tidal expiration
FEVI = forced expiratory volume in one second. 80% of vital capacity in healthy person.
FVC = forced vital capacity (the amount of air that can be forcably exhaled from the lungs. Does not include alveolar dead space. TLC does). Ie max air exhaled after max vol inhaled using max force.
PEF (peak air flow): max velocity of air during FVC. In a healthy person, velocity should decrease linearly after PEF.
FVC = TLC - RV
Note:
FEV1/FVC > 0.8, ordinarily.
55
What is the use of a spirometer?
Measures PEF. Readings in L/min.
In airway obstruction: reduced airflow leading to hyperinflation, decreasing FEV1 but increasing RV & TLC. FVC remains similar, ratio of FEV1/FVC reduced to below 0.7. ‘Scalloped’ flow loop. E.g.: COPD, asthma
In airway restriction: reduced compliance of lungs, reducing both FEV1 and FVC. Ratio remains the same but all other parameters reduced (VC, IC, EC. E.g.: pulmonary fibrosis
56
What are ways of measuring lung vol?
Expiratory procedure only measure VC, not RV.
Other methods are required to measure RV and TLC.
These are gas dilution and body box.
57
How can gas dilution measure lung volume?
Measures TLC.
Ask the patient to breathe in a known conc of gas.
The change in conc of the gas after being breathed back out is a function of the volume of the lungs.
May not work if a section of the lung isn't being ventilated.
58
What are the 7 layers of gas exhange?
1. Fluid lining alveolus
2. Layer of epithelial cells – type I pneumocytes
3. Basement membrane of type I cells
4. Interstitial space
5. Basement membrane
6. Endothelia
7. Erythrocyte
59
How does the total body plethysmography?
Patients are locked into a box and are (often) asked to pant/ hyperventilate).
Oscillations in the pressure in the box allow measures of lung volume.
60
What is a transfer estimate?
TLCO - the best estimate of lung volume.
Considers alveolar surface area, alveolar capillary perfusion, capillary volume, Hb concentration and many more factors.
It is done by 10 second breath hold (10% He, 0.3% CO, 21% O2, remainder N2).
Considers change in CO concentration.
61
Summarise control of breathing
62
What are the major respiratory control centres?
In the pons:
Principally pneumotaxic and Apneustic centres. These are responsible for phasic discharge.
In the medulla oblongata:
DRG (dorsal respiratory group) and the VRG (ventral respiratory group). These generate the phasic rhythmic breathing - the breathing pattern generation. The exact function is not known.
The DRG is primarily inspiration focussed.
The VRG is active in inspiration and expiration.
Each are bilateral and project into the bulbo-spinal motor neurone pools and interconnect.
63
How is inspiration controlled?
Progressive increase in inspiratory muscle activation
Lungs fill at a constant rate until tidal volume is achieved. At the end of inspiraton, there is a massive decrease in excitation of respiratory muscles.
"The brakes are put on"
64
How is expiration controlled?
Largely passive due to elastic recoil of thoracic wall.
Further muscle activity is activated with increased demands.
65
How do chemoreceptors control breathing?
Central receptors found at pontomedullary junction in the brainstem.
Peripheral receptors in bifurcation of carotid arteries (CNIX) and in aortic arch (CNX)
In arterial blood (aorta and carotids), primary influences are PaCO2, PaO2 and pH.
In the brainstem, primary influence in CO2.
66
Describe the central chemoreceptors influence on breathing rate
Respond to CO2 changes alone.
Located in brainstem at the pontomedullary junction, but not within the DRG/ VRG complex.
In the CSF, diffused PaCO2 influences breath ability.
They are not sensitive to H+ in the blood as the blood brain barrier is relatively impermeable to H+.
CO2 diffuses.
Carbonic acid buffer shifts in the CSF. This produces more H+, which causes the stimulus to breathe.
67
Where are the peripheral chemoreceptors for breathing?
In the carotid bodies:
- At the bifurcation of the common carotid.
- IX cranial nerve afferents
In the aortic bodies:
- Ascending aorta
- Vagal (X) nerve afferents.
68
How do the peripheral chemoreceptors influence breathing?
They are responsible for all response to hypoxia.
They generally only fire at low levels of oxygen. They try to adapt to increase PAO2.
When exposed to hypoxia, the type I cells release stored neurotransmitters that stimulate the cuplike endings of the carotid sinus nerve.
No peripheral receptor response if hypocapnic even if hypoxic, and no response to acidosis if hyperoxic.
Prolonged hypoxia can cause type II sustentacular cells to differentiate in to type I to increase AP firing to further stimulate ventilation.
69
What
70
What are abnormal PaO2 and PaCO2 levels?
PaO2 < 8kPa
PaCO2 > 6.5kPa is hypercapnic
71
What are the two types of respiratory failure?
Type I - hypoxia and hypocapnia / normal CO2. Can be caused by infection, airway, vasculature.
Type II - hypoxia and hypercapnia. Caused by airway, drugs, muscle, neurological.
72
What does an O2 mask do?
Increases FiO2.
73
What are some symptoms of hypercapnia?
Warm, headache, bounding pulse, papilloedema.
74
How is NO used in clinical practice?
Exhaled NO can be measured by a simple machine.
Measured in ppb.
Normal < 25 ppb.
High > 50 ppb.
Generally increased in asthma, though it is not diagnostic.
It provides a reflection of eosinophilic airway inflammation.
75
What are common occupational causes for asthma?
High molecular weight allergens:
- Grain
- Wood
- Animals and fish
- Latex
Low molecular weight allergens:
- Gluteraldehyde
- Isocyanates
- Paints
- Metal working fluids
- Metals
76
Define asthma
Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction and bronchospasm.
Common symptoms include wheezing, coughing, chest tightness, and shortness of breath.
77
Describe prevalence of asthma
5-16% of people worldwide have asthma, with a wide variation between countries.
Increased in prevalence in the 2nd half of the 20th century, but now mostly plateaued.
US study identified cases were higher in poorer individuals and African Americans.
78
What are risk factors for asthma?
Many studies have identified a wide range of risk factors for asthma, including thunderstorms, which stir up pollen.
It was also identified that people with no cats or a large number of cats were less likely to develop asthma.
Air pollution and the quality of air you breathe are very important. Responses to pollutants can be analogous to viral responses.
Asthma admissions relate closely to PM2.5 and PM10 (microns of diameter of particulate matter).
Increasing evidence to suggest that NO exposure in the first year of life can lead to increased pollen sensitivity by the age of four.
79
What is hypersensitivity pneumonitis?
An inflammation of the alveoli caused by hypersensitivity to inhaled dusts.
There are acute, sub acute and chronic forms.
Significant environmental influences. links to farmers lung, bird fanciers lung, metal working fluids.
80
What is animportant thing to ask a patient presenting with respiratory problems?
About hobbies. Various things like working with animals, playing a reed instrument or going into hot tubs can be the things cuasing the respiratory issue.
81
What is COPD?
Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by chronically poor airflow. It typically worsens over time, with the main symptoms include: shortness of breath, cough, and sputum production.
The commonest cause is tobacco smoking, but has a range to environments, and occupational risk factors.
Ie exposure to:
Silica, Coal, Grain, Cotton, Cadmium.
82
Describe lung function trajectories
83
How is asthma inherited?
It does run in families.
Transmission through generations does not follow simple mendelian inheritance typical of classic monogenic diseases.
It is controlled by multiple genes on many different chromosomes (ie 2, 6, 9, 15, 17 and 22)
84
What is cystic fibrosis?
A condition that causes thick mucus to build up in the lungs and many other organs.
Multiple organs are involved and affected.
It is the most common lethal autosomal recessive genetic disorder in Caucasians, though the median age of death is improving.
In 80% of cases, the lung and GI systems are affected.
15 % of cases affect the lung alone.
1 in 25 are carriers. 1 in 2500 prevalence.
85
How is cystic fibrosis caused?
Autosomal recessive inheritance.
By a defect in a gene in the long arm of chromosome 7 which codes for the cystic fibrosis transmembrane regulator protein (CFTR protein). It is an anion channel.
There are >1600 mutations of CFTR that have been identified. 90% are within 70 mutatuons.
The most common is the F508del mutation.
86
What is the CFTR protein?
A transport protein on the membrane of epithelial cells which moves chloride ions out of the cell. Abnormal CFTR proteins don't move chloride ions, causing sticky mucus to build up on the outside of the cell.q
87
How does CF affect different organs?
Pancreas: excess mucus blocks endocrine ducts, early activation of pancreatic enzymes, eventual auto-destruction of the exocrine pancreas (supplemental pancreatic enzymes required for patient).
Intestines: increased mucus builds bulky stools, leading to intestinal blockage.
Respiratory system:
Mucus retention, chronic infection, inflammation that destroys lung tissue.
88
How can CF be classified by genotype?
Class I: no functional CFTR protein is made (e.g. G542X)
Class II: CFTR protein is made but it is mis-folded (e.g. F508del). The F508del is the most common mutation. Affects 80-90% of patients.
Class III: CFTR protein is formed into a channel but it does not open properly (e.g. G551D)
Class IV: CFTR protein is formed into a channel but chloride ions do not cross the channel properly (e.g. R347P)
Class V: CFTR protein is not made in sufficient quantities (e.g. A455E)
Class VI: CFTR protein with decreased cell surface stability (e.g. 120del123)
Class II and III are the main ones. Make sure you can remember them.
89
What is the general treatment strategy for CF?
Maintenance and prevention management
Rescue antibiotics when infection
Personalised approaches. Stratified based on predicted response or risk of disease. Genetic information is a major factor.
90
Provide some drugs used to treat CF
Orkambi is licensed for use in F508del mutations in the UK. Used for class II.
Ivacaftor is a CFTR potentiator. It potentiates chloride secretion by increasing the CFTR channel opening time. Used for Class III mutations.
91
What are some challenges of treating CF?
Adherence to treatment.
High treatment burden.
High cost of certain treatments.
Allergies and intolerances to treatments.
Different infectious organisms and their resistance to drugs.
92
What is Alpha-1 antitrypsin deficiency?
AATD, an autosomal recessive genetic disorder.
80 different mutations of SERPINEA1 gene on chromosome 14 can cause the deficiency.
It codes for a serum antiprotease to inhibit neutrophil elastases.
The M pehnotype is normal and healthy
The S and Z phenotypes have major disease associations.
It causes early onset emphysema and bronchiectasis due to damage of elastin that maintains conducting airway strcuture.
Increased risk of de novo mutation with smoking.
93
Provide the equal pressure measurements for 1 atmospheric pressure.
1atm
1bar (1000 millibars)
760 mmHg / torr
1 ATA (atmosphere absolute)
10 metres of sea water (msw)
33.08 ft of sea water (fsw)
101.3 kPa
14 psi
94
How much does pressure increase when you go deeper in water?
10m of water = 1 added ata
ie 20m down = 3ata (NOT 2ata).
95
What is boyle's law?
At a constant temperature, the absolute pressure of a fixed mass of gas is inversely proportional to it's volume.
P1V1 = P2V2
Applications:
Barotrauma
arterial gas embolism
gas supplies
96
What is Henry's Law's application to diving at depth?
More gas will dissolve into the tissues at a greater depth.
97
What is the diving reflex?
Upon immersion of the face in water (normally in cold water) the body has a series of involuntary physiollogical processes happen, which can cause death.
Apnoea
bradycardia
peripheral vasoconstriction
98
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.
This means that breathing air at 10msw is the same PaO2 as breathing 42% O2 at sea level.
99
What is the Lorrain Smith effect?
Pulmonary oxygen toxicity.
When PiO2 > 0.5 ATA.
- On 100% oxygen, symptoms begin within 12-24 hours.
- Symptoms include cough, chest tightness, chest pain, shortness of breath.
- This is an issue that must be considered with ITU patients.
Relief when PiO2 < 0.5 ATA.
UTPD (unit of pulmonary toxic dose) can be calculated.
Divers must balance oxygen correctly to avoid this.
100
What is CNS oxygen toxicity?
Another type of oxygen toxicity.
Characterised by ConVENTID.
Con = convulsions (often first sign)
V = Vision (tunnel vision etc)
E = ears (tinnitus)
N = nausea
T = twitching (extremities or facial muscles)
I = irritability
D = dizziness
101
What is inert gas narcosis?
Where certain gases at high pressure cause an anaesthetic effect that affects a diver's consciousness.
Commonest is nitrogen narcosis.
Worsens with increasing pressure. First noticed at 30-40 msw.
Caused from increased PiN2. High levels cause increase in gas lipid solubility. Gas dissovles in cells of the brain. Causes effects similar to being drunk and stupefaction.
Influencing factors include cold, anxiety, fatigue, alcohol and drugs etc.
Loss of consciousness and death below 90m.
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What is decompression sickness?
N2 is poorly soluble. It takes time to dissolve in and out of tissues and blood. Quick ascent causes dissolved gases to expand in the blood and tissues.
Type I and type II, based on severity.
Type I is the less severe, characterised by a rash and joint pain.
Type II can lead to neurological impairment.
Can also lead to arterial gas embolism.
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What is arterial gas embolism?
Caused from an example like a breath hold, then ascent.
Gas tries to expand, and enters circulation via torn pulmonary veins. Boluses of gas can collect in arteries and veins and cause an embolism.
Normally occurs within 15 minutes of surfacing.
Urgent recompression required for treatment.
(can also be a result of decompression sickness)
104
What happens to oxygen levels when you increase in altitude?
FiO2 stays constant.
PiO2 decreases.
105
How do we find the PiGas?
Patm x FiGas
ie at sea level, Pio2 = 100kPa x 0.21 = 21 kPa at sea level.
106
What are the two gas equations used?
PAO2 = PiO2 - PaCO2 / R
R= 0.8 in a healthy individual
PaCO2 = kVCO2 / VA
107
Show normal barometric pressures at increased altitudes.
108
What is A-aDO2?
The difference in alveolar and arterial oxygen partial pressures.
Normally 1kPa or less.
= PAO2 - PaO2 = approx 1kPa
109
Show normal blood gases
PaO2 10.5-13.5 kPa
PaCO2 4.5 - 6.0 kPa
pH 7.36 - 7.44
110
Describe the oxygen dissociation curve
Shifts to the right with decreased pH/
111
At what altitude does hypoxia occur?
Around 10,000 ft.
Peripheral chemoreceptors cause hyperventilation due to low PaO2.
Characterised by hyperventilation (leads to lower PaCO2 and tachycardia leading to initial alkalosis).
Alkalosis is compensated by renal bicarbonate excretion.
112
What is acute mountain sickness?
Caused by a recent a rapid ascent to over 2500m.
It can only reliably be treated with descent.
Characterised by the presence of a headache and at least one other symptom (GI issues, dizziness, sleep issues, fatigue).
Can lead to high altitude pulmonary oedema and high altitude cerebral oedema.
113
Describe high altitude pulmonary oedema (HAPE).
Symptoms are cough, shortness of breath.
Caused by a rapid ascent to over 8000ft.
Indicated by cough, frothy sputum and breathlessness.
DESCENT IS PRIMARY TREATMENT
Treatments include:
- O2
- Gamow bag
- Steroids
- Ca2+ blockers
-Sildenafil
114
Describe high altitude cerebral oedema (HACO).
Serious - immediate descent required. Symptoms may resolve relatively quickly.
May or may not have had acute mountain sickness.
Characterised by confusion, behaviour change.
115
What is the pressure in aircraft?
Effective capin atmosphere = 1890m
cabin pressure = 81kPa
Patients with O2 sat < 92% require O2 supplements to fly.
116
What are the stages of lung development?
Embryonic - 0-5 weeks
Pseudoglandular - 5-17 weeks
Cannalicular - 16-25 weeks
Alevolar - 25 weeks to term.
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From what do the lungs develop? (embryonic development)
They are a foregut derivative.
A diverticulum that grows off of the oesphagus.
118
Describe pseudoglandular development of the lungs.
5-17 weeks.
Development of the conducting airways.
They are filled with fluid, pretty much until term.
119
Describe cannalicular development
16-25 weeks.
The lungs cannalise - capillaries, vasculature and alveoli form.
120
Describe alveolar development
25 weeks to birth
development of alveolar sacs
Development of type 1 and type 2 cells.
Alveoli continue to develop up to the age of 5.
Surfactant production begins around week 34. This reduced surface tension and allows equal aeration of alveoli.
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Summarise what can go wrong in lung development
Embryonic:
Laryngeal, tracheal and oesophageal atresia. Tracheal and bronchial stenosis. Pulmonary agenesis. Tracheoesophageal fistula.
Pseudoglandular:
Bronchipulmonary sequestration, cystic adenomatoid malformatios, alveolar-capillary dysplasia.
Alveolar:
Acinar dysplasia, alveolar capillary dysplasia, pulmonary hypoplasia, respiratory disease of the newborn.
122
What is tracheoesophageal fistula?
Where the trachea and the oesophagus become attached.
123
What are cystic adenomatoid malformations?
In early pseduoglandular phase.
124
How does the effects of oxygen on vessels in systemic and pulmonary circulation?
In systemic circulation, oxygen is a vasoconstrictor. Hypoxia, acidosis, CO2 are vasodilators. This increases perfusion of blood vessels, so there is improved oxygenation.
In pulmonary vessels, oxygen in a vasodilator. Hypoxia, acidosis, CO2 are vasoconstrictors. Why would you want to send blood to a hypoxic part of the lung? This increases oxygen delivery.
125
How do type II pneumocytes prepare for the first breath?
They contain NKCC and apical Cl- channels to actively fill the lungs with fluid. The fluid aims for lung development.
126
What are the 3 shunts in the foetus?
- Ductus venosus: a shunt that allows oxygenated blood in the umbilical vein to bypass the primitive liver. It is essential for normal foetal circulation. It diverts about 1/3 of the oxygenated blood and diverts it into the IVC.
- Ductus arteriosus: between pulmonary trunk and aortic arch. Bypasses the lungs. Closes rapidly at birth by muscular contraction (as mediated by bradykinin).
- Foramen ovale: RA to LA. Bypasses the lungs. Closes at birth.
At birth, they all change/ close very rapidly to close.
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What happens at birth?
The tight squeeze through the uterus squeezes the fluid out of the lungs. The cough reflex is initiated to further expel fluid. Some fluid is absorbed into circulation.
Surfactant production increased.
Entry of O2 into lungs causes decreased pulmonary circulation pressure (as O2 is a pulmonary vasodilator).
Right atrial pressure falls - foramen ovale closes.
Umbilical arteries constrict.
Ductus arteriosus constricts, under changes in O2 and bradykinin.
These changes happen rapidly.
128
How does blood pressure change at birth?
Before birth, R heart pressure is higher.
Rapid switch to L heart high pressure system, R low.
129
How might premature neonates have issues?
Premature neonates may suffer with respiratory distress syndrome due to underdeveloped acini, bronchopulmonary dysplasia or specifically a lack of type II pneumocytes (collapse of alveoli due to insufficient surfactant).
130
What is Laplace's Law?
Larger alveoli may preferentially open as smaller alveoli preferentially shut with a given surface tension. Surface tension is essential for keeping smaller alveoli patant.
131
What happens if a baby is born without surfactant?
Asphyxia
Cold
Stress
They can develop respiratory distress syndrome.
Can have loss of lung volume.
To treat, you may need ventilation, steroids or adrenaline (to imporve production).
132
What is eisenmenger's syndrome?
Centricular septum defect causing intracardiac shunt, blood continues to bypass pulmonary circ. after birth. Causes cynosis, clubbing, polycythemia (raised haematocrit).
133
What regulates the size of airways?
The autonomic nervous system. Contractile signals cause an increase in intracellulsr calcium in the smooth muscle, which activates actin myosin contraction. This leads to airway relaxation.
It is also regulated by inflammation (asthma, copd). Causes bronchoconstriction.
The pre and post ganglionic fibres relay information.
134
What is a difference between the somatic and autonomic nervous system?
Somatic only have a single ganglion. They synapse once, at the effector organ.
Autonomic fibres are comprised of two neurones separated by an autonomic ganglion:
Parasympathetic fibres synapse into a ganglion far from the CNS, close or within the effector organ.
Sympathetic fibres synapse close to the CNS.
The smpathetic and parasympathetic systems use different neurotransmitters.
135
How is bronchoconstriction controlled?
Parasympathetic stimulation.
Branches of vagus (VIII) nerve.
Short, post synaptic nerve fibres reach the muscle and release acetylcholine, which acts on muscarinic receptors of the M3 subtype of the muscle cells.
This stimulates muscle constriction.
Drugs can block the M3 receptor, and block the parasympathetic nerve effect in the organ. Bronchodilatation.
136
What are LAMAs and SAMAs?
Long acting muscarinic antagonists and short acting antimuscarinics. Example is ipratroipum. They regulated parasympathetic stimulation of the lungs/ bronchus.
Drugs that block the M3 receptor for a longer/ shorter time.
Some drugs also have other benefits, like parasympathetic regulation of mucus production.
137
How is sympathetic stimulation registered generally?
There are alpha and beta adrenergic receptors in the airway smooth muscle. Nerve fibre release of noradrenaline activates these receptors
138
How is sympathetic stimulation registered in the airways?
Airways have beta2 adrenergic receptors. Activation of these by noradrenaline causes muscle relaxation, bronchodilation.
139
What are SABA and LABAs?
Short acting (salbutamol) and long acting (formoterol) beta2 agonists.
Given in treatment for asthma and COPD.
Useful in acute rescue of bronchoconstriction.
Prevention of bronchoconstriction.
Reduction in rates of exacerbations.
140
What are some side effects of B2 agonists?
They raise cAMP. This may activate Na/K exchange, driving cellular influx of K+. This can lead to hypokalemia. Can be used in treatment of hyperkalemia.
Tachycardia.
Overactivation of B2 receptors due to loss of insulin senstivity and increase in liver glucose release -> hyperglycaemia.
141
What is hypersensitivity?
Gell and Coombs classification, c1960:
The recognition that foreign antigens can cause collateral tissue damage.
Imperfect, does not hold for complex immune reactions.
They said there were 4 types of hypersensitivity.
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Describe type 1 hypersensitivity
Allergy, anaphylaxis and atopy.
Mediated by IgE antibodies, an acute response.
The antigen interacts with IgE bound to mast cells or basophils in the airways. Systematic degranulation of mast cells (most significantly histamine release and other mediators), causing vasodilation and opening of gap junctions.
Can lead to bronchospasm as a result of histamine in the airways.
Come on within an hour of infection.
Adrenaline most important.
Examples include anaphylaxis and hayfever. Histamine is the predominant mediator.
Note: mast cells also release delayed mediators after a few hours, can cause a second spike of anaphylaxis.
Can be identified using the skin prick test.
143
Describe type II hypersensitivity.
Cytotoxic antibodies that bind to cell antigen.
Usuaully IgG or IgM binding to body's own antigens (autoimmune).
Causes a range of responses like cell lysis, neutrophil activation and tissue damage.
Hours to days.
Examples are transfusion reactions.
144
Type III hypersensitivity
Deposition of immune complexes.
On expsoure to the antigen, immunoglobulin attaches itself to the antigen forming an antigen immunoglobulin complex.
They are deposited in tissues and cause local activation of complement system and neutrophil attraction to the site (secondary organ inflammation).
7-21 days typically.
Examples hypersensitivity pneumonitis. In this, the deposits end up in the lungs and cause airway inflammation. Long term, causes lung scarring.
145
Type IV hypersensitivity
Mediated by T cells (lymphocytes), releasing IL2, IFy and other cytokines.
If the macrophages cannot defeat the pathogen, T helper cells form granulomas around pathogens with macrophages in a cell-mediated response not involving antibodies.
It requires a primary sensitisation, and the secondary reaction takes 2-3 days to develop.
Takes days, weeks or months to come about.
Eg Stevens-Johnson syndrome, Tuberculosis.
146
What is Goodpastures disease?
Aka glomerular basement membrane disease.
A type of type II hypersensitivity classification.
It describes alveolar haemorrhage.
In this disease, alpha 3 subunit of type IV collagen becomes antigenic - the body develop GBM antibodies against it.
The basement membrane of the airways becomes undeveloped, leaking of fluid into the alveoli.
147
What is mycoplasma pneumonia?
Another type of type II hypersensitivity.
It causes an atypical pleumonia. The epitopes of the mycoplasma are similar to the i antigen of red cells. This causes the agglutination and haemolysis of red cells.
148
What are the different types of asthma?
Eosinophilic and non-eosinophilic.
