Systems 2 - Respiratory Flashcards
(200 cards)
1
Q
Respiration definition
A
-O2 from atmosphere delivered to cells of body -enables cells to produce energy by oxidative reactions -the by-product, CO2, is removed to atmosphere
2
Q
Trachea structural features - Cartilage
A
Supporting C circles of hyaline cartilage
Provide structure
Incomplete ring, so bolus can pass through oesophagus in swallowing
3
Q
Trachea structural features - Cells
A
Pseudostratified ciliated epithelium
Goblet cells for mucus production
-> Together, mucociliary escalator to beat mucus to back of throat where it can be swallowed, goes to acidic stomach
4
Q
Bronchioles structural features
A
No cartilage, patency maintained by connective and elastic tissue’s radial traction of lung
Lots of smooth muscle, for bronchoconstriction/dilation
Diameter > 1mm
Ciliated simple columnar epithelium in conducting (= terminal) bronchioles
Ciliated simple cuboidal epithelium in respiratory bronchioles
5
Q
Alveoli structural features
A
Walls 0.5μm thick, only simple squamous eptheilium
Large surface area, mainly filled with capillaries for gas exchange
4 cell types- type I and II pneumocytes, alveolar macrophages and red blood cells
6
Q
Cells in alveoli
A
TYPE I PNEUMOCYTES
- large, flat surface for gas exchange
- 90% of SA of alveoli
- tight junctions
- cell wall fused to capillary endothelium
TYPE II PNEUMOCYTES
- secrete surfactant to reduce surface tension
- only produced after 24 weeks gestation, so ‘respiratory distress of the newborn’ if premature
ALVEOLAR MACROPHAGES
- to mop up foreign tissue present
RED BLOOD CELLS
7
Q
Functions of the airway
A
Primary
- conducting zone to deliver air to site of gaseous exchange
- respiratory zone to carry out gaseous exchange
Secondary
- humidify and warm air
- protect against particulates and infection
As the diameter of individual airways decreases, SA for gas exchange increases
8
Q
Measurement of Functional Residual Capacity
A
Fill spirometer bell and tubing with 10% Helium (He doesn’t dissolve in body tissues but stays in gas filled spaces of lungs)
C₁ x V₁ = C₂ x (V₁ + V₂)
1 = conc/volume of He in spirometer and tubing before equilibration C₂ = conc of He in new increased volume (V₂ also) V₂ = volume of air in lungs
Therefore FRC = (Volume in spirometer x ([He} at start - [He} at end)) / [He} at end
9
Q
Residual volume
A
Residual Volume = Functional residual capacity - End residual volume
10
Q
Anatomical dead space
A
The volume of gas in collecting airways (so not taking part in gas exchange)
Measured using Fowler’s method:
- subject inhales single breath of 100% O₂
- expires breath into nitrogen meter
- initial air has 0% nitrogen as is from dead space air just breathed in
- then nitrogen content rises as alveolar air mixes
- draw line down curve to get approx. 2.2 ml/kg nitrogen
11
Q
Physiological dead space
A
The total volume of gas in the system not taking part in gas exchange.
Measured using Bohr method:
- measure first air expired (dead space) for CO₂ conc
- measure last air expired (alveolar) for CO₂ conc
Volume dead space/Tidal volume = Fraction alveolar CO₂-Fraction expired CO₂/Fraction alveolar CO₂
Approx 165ml is dead space, 1/3 of tidal volume
Pulmonary embolism increases dead space - more ventilation without perfusion
12
Q
Estimated dead space (ml)
A
2.2 x body weight (kg)
Usually approx 165ml, 1/3 of tidal volume
13
Q
Minute volume
A
Volume of gas breathed in or out per minute
Minute volume = Tidal volume x frequency
14
Q
Alveolar ventilation
A
(Vt-Vd) x frequency
15
Q
Fraction of alveolar CO₂
A
Fraction of alveolar CO₂ ∝ Rate of production of CO₂ / Alveolar ventilation
16
Q
Correcting volume for different conditions
A
V₂ = V₁ x T₂/T₁ x P₁/P₂
To correct for pressure and temperature
17
Q
Pressures in lung lining
A
Lung pulls into centre due to elastic recoil
Chest walls pulls out due to elastic recoil
-> Pleural sac in between therefore has negative intrapleural pressure
18
Q
Boyle’s law
A
Pressure ∝ 1/Volume
for a given quantity of gas in a container.
(Pressure is inversely proportional to Volume. Also written PV=K where K is a constant.)
19
Q
Process of inspiration
A
Diaphragm flattens and moves down
Contraction of external intercostal muscles so ribs move up and out
- > increased volume in thoracic cavity
- > decrease in alveolar pressure
- > air moves in until alveolar pressure = atmospheric pressure
20
Q
Process of expiration
A
Passive expiration in normal quiet breathing:
lungs recoil, decrease in lung volume, increase in alveolar pressure
In forceful expiration, abdominal muscles and internal intercostals contract
At FRC, recoil of lungs is balanced with recoil of chest walls, so only need forceful expiration past FRC.
21
Q
Pneumothorax
A
Air in thorax, usually from trauma when chest wall is damaged
Chest wall becomes separated from lung, so -> collapsed lung (will appear on CXR as mediastinal shift away and absent vascular markings)
22
Q
Work of breathing
A
30% for airway resistance
65% for compliance (elasticity of lung)
5% functional resistance
23
Q
Airway resistance
A
Determines flow of gas through system
Q= ΔP/R
Flow = change in pressure/resistance
Upper airways have most resistance, smallest airways have low resistance, as they have the greatest total cross sectional area
24
Q
Pouiselle’s law, airway resistance
A
Resistance of tube = (8 x viscosity x length) / π x radius⁴
25
To measure airway resistance
Airway resistance = FEV₁/FVC
= Forced expiratory volume in one second / forced vital capacity
Should equal or exceed 80% in a healthy person
26
Vitalograph
Breathe out as hard and fast as possible into machine
-\> Produces curved graph of volume over time
FEV₁ can be found by 1s along up to volume
FVC is plateau point at maximum volume
-\> Then can find FEV₁/FVC, so airway resistance
27
Peak expiratory flow
Can be found by steepest point of vitalograph (first section)
Changes with age and height, but should be approx 420ml for women, 600ml for men
If less than 80% of expected PEF -\> amber
If less than 50% -\> red, probable airway resistance
28
Airway resistance decreased by
Sympathetic nervous system activity, altering smooth muscle tone, dilation of airways
Increased lung volume, pulling open airways by radial traction
Increased CO₂ concentration
29
Pathophysiological changes to increase airway resistance
ASTHMA - increased constriction of smooth muscle in bronchioles, increased mucus secretion, inflammation
COPD
- Bronchitis - Increased mucus, inflammation
- Emphysema - Decreased pulmonary tissue, so decreased radial traction, airway collapse, decreased elastic recoil of lungs, INCREASED FRC as airway size increases, but airway more collapsible, harder to hold open
PULMONARY OEDEMA - eg left sided heart failure
30
COPD diagnosis (ratio)
Obstructive, so decreased rate at which air can leave the lungs
Lower FEV₁/FVC ratio
31
Compliance
A measure of the elasticity of the lungs, the ease with which they can be inflated
Compliance = Change in lung volume (ΔV) that results from a given change in transpulmonary pressure (Pressure in alveoli - interpleural pressure)
Compliance = ΔV/ΔP
With increased compliance, there will be an increased change in lung volume for a given increase in transpulmonary pressure.
32
Pressure-Volume curve
As pressure around the lung rises (becomes for negative), lung volume increases
Different inward and outward tracks (to do with surface tension)
Can measure intrapleural pressure by putting balloon in oesophagus. Oesophagus is floppy so exposed to pressures in thorax.
33
Regional effect of gravity on lung ventilation
Higher pressure at top of lung than at bottom -\> so more distended at top
Different regions of lung work at different points in the compliance curve
-\> so more ventilation at bottom than at top of lung
34
Compliance depends on
Elasticity of lungs
- elastic fibres in connective tissue exert force opposing lung expansion
- a build up of collagen stiffens lung
Surface tension of fluid lining alveoli
- traction between liquid molecules pulls alveoli closed
35
Law of Laplace, relevance to alveolar filling
P = 2T/r
Air pressure inside alveolus = 2 x surface tension / alveolus radius
Therefore if small and large alveoli had the same surface tension, small alveoli would not fill as they would have higher pressure, and would collapse into larger alveoli, creating an unstable structure.
Surfactant stops this, stabilises the structures by decreasing surface tension
36
Surfactant
Phospholipid
Produced by type II pneumocytes
Decreases surface tension - more surfactant in smaller alveoli, so equal pressure in large and small alveoli.
Increases the compliance of the lungs, decreasing the work of breathing
If born premature (pre 24 weeks), deficient surfactant so newborn respiratory distress syndrome.
37
Factors increasing compliance
Emphysema - increases lung volume
Ageing
38
Factors decreasing compliance
Fibrosis - decreases lung volume
Surfactant deficiency
39
Restrictive lung disease
Decreases FRC
eg fibrosing alveolitis - increased collagen in lung, so thickened membrane, stiffer lung, harder to increase volume
40
Pulmonary circulation
Same volume pumped from left and right ventricles
- but lower pressure in pulmonary system
- so must have decreased resistance
Higher bp in bottom of lung than top, as more ventilation here
Due to low pressure pulmonary artery, gravitates to bottom of lung
41
Anatomical shunt
Deoxygenated blood added to systemic circulation
~2% in health, increased in pathology (eg if lung not ventilated)
Intrapulmonary - some capillary pathways don't go in via alveoli
Deep bronchial veins - to supply lung tissue
Thebesian circulation - to supply cardiac tissue
All drain into pulmonary vein or left heart, already deoxygenated
42
Calculation of shunt
Qs / Qt = (CcO₂ - CaO₂) / (CcO₂ - CvO₂)
Blood flow through shunt/total blood flow = (Pulmonary capillary O₂ content - arterial O₂ content) / (Pulmonary capillary O₂ content - venous O₂ content)
43
Shunt and dead space
Neither take part in gas exchange
SHUNT- blood flow but no O₂
DEAD SPACE- ventilated but no blood flow
44
Hypoxic vasoconstriction
Decreased PAO₂ -\> local vasoconstriction, diverting blood away from poorly ventilated alveoli
Beneficial, helps ventilation as perfusion matching important in foetus.
Bad when large areas of lung have low PAO₂, eg at altitude or in chronic hypoxic lung disease.
45
Calculating partial pressures of gas
DRY GAS:
Pgas = Ptotal x Fgas
SATURATED:
Pgas = (Ptotal - Ph₂o) x Fgas
46
Henry's law, volume of dissolved gas
Volume of dissolved gas = volume of blood x stability of gas x Pgas
Pgas is measured at the equilibrium of tendency of gas to leave vs tendency to enter liquid.
47
Rate of diffusion of gases influencing factors
Rate is proportional to
- size of concentration gradient
- surface area of membrane
- permeability of membrane to particular substance
48
Clinical test for diffusing capacity
- one breath of 0.3% CO
- hold for 10s
- measure CO conc in expired air
- determine how much CO has diffused into lung, giving volume of CO transferred in ml/min/mmHg of alveolar partial pressure
Typically around 25ml/min/mmHg Lower than this indicates problem with gas exchange
49
Ventilation-Perfusion ratio
VA/Q = ventilation per unit blood flow
More blood flow and ventilation at the bottom of the lung, where there is the lowest VA/Q (not ideal)
If you block ventilation, VA/Q decreases, as composition of venous blood = arterial blood
If you block blood flow, VA/Q increases, as composition of expired gas = inspired gas
50
Expenditure of O₂
Breathe in 150mmHg O₂ in air
Decreases in alveoli, added to dead space, humidified V/Q inequalities and diffusion
Shunt in arteries
Loss to tissues
Venous blood 40mmHg
51
Alveolar-Arterial difference
PAO₂ \> PaO₂ due to physiological shunts
PAO₂ calculated with alveolar gas equation, PaO2 measured in sample of arterial blood
Can be used in differentiating causes of hypoxia
52
Alveolar gas equation
PAO₂ = PIO₂ - PAO₂/RQ
53
Cause of hypoxia differentiation - High Altitude
Low PAO₂
Low PaO₂
Normal A-a difference
O₂ therapy beneficial
54
Cause of hypoxia differentiation - Hypoventilation
Low PAO₂
Low PaO₂
Normal A-a difference
O₂ therapy beneficial
55
Cause of hypoxia differentiation - VQ mismatch
Normal PAO₂
Low PaO₂
Increased A-a difference
O₂ therapy beneficial
56
Cause of hypoxia differentiation - Shunt
Normal PAO₂
Low PaO₂
Increased A-a difference
O₂ therapy limited benefts
57
Cause of hypoxia differentiation - Diffusion defect
Normal PAO₂
Low PaO₂
Increased A-a difference
O₂ therapy beneficial
58
CO₂ output
CO₂ output = (Volume expired x Fraction expired CO₂) - Volume inspired x Fraction inspired CO₂)
Usually around 200ml of CO₂ at rest
59
O₂ uptake
O₂ uptake = (Volume inspired x Fraction inspired O₂) - (Volume expired x Fraction expired O₂)
Usually around 250ml of O₂ at rest
60
Measuring O₂ consumption with a spirometer
- drum filled with 100% O₂
- soda lime used to remove CO₂ from exhaled air
-\> can measure the rate of loss of O₂, rate of consumption
61
Respiratory quotient
RQ= CO₂ output / O₂ uptake
Should be 0.8 under resting conditions (200/250)
Changes with substrate:
0.7 Fat
0.8 Protein
1 Carbohydrate
62
Carriage of O₂ in the blood
Each 100ml of arterial blood is approx 20ml O₂
In solution and with haemoglobin
63
O₂ in solution
PO₂ relatively high (PaO₂ = 100mmHg)
BUT O₂ not very soluble (0.003ml O₂/100ml blood/mmHg PO₂) -\> at PO₂ of 100mmHg, 100mls of blood contains 0.3ml of O₂ in solution
64
O₂ with haemoglobin
Majority of O₂ carried this way
Hb has 4 interlinked polypeptide chains (2 alpha, 2 beta)
Each chain binds to a haem group, which each contain Fe²⁺
Each haem group binds one O₂ molecule, so one Hb has four O₂s
Foetal haemoglobin has a lower PO₂, so an increased affinity for O₂ due to different polypeptides.
65
Reversible binding of O₂
High PO₂, binding
Becomes oxyhaemoglobin, and then diffuses down concentration gradient to tissues with low PO₂
Low PO₂, release
Deoxyhaemoglobin is dark purple, oxyhaemoglobin is bright red
66
Oxygen content of blood calculation
O₂ content = ([Hb} x 1.34 x % saturation) + (PO₂ x 0.003)) ml O₂/100ml blood
In arterial blood, around 20ml O₂/100ml blood
67
PaO₂ SaO₂ CaO₂
Partial pressure of O₂ dissolved in blood, mmHg
Percentage saturation of Hb with O₂, %, sigmoidal relationship to PaO₂
Total volume of O₂ contained per unit volume blood, ml/100ml
68
Oxyhaemoglobin dissociation curve
Sigmoidal
Binding O₂ increases the affinity to bind another, due to conformational change in the molecule
69
Affinity of haemoglobin for O₂
Sigmoidal curve shifts
To left - increase affinity, O₂ loaded more easily (foetal)
To right - decrease affinity, O₂ unloaded more easily
70
Factors decreasing haemoglobin's affinity for O₂
SHIFT TO RIGHT
Increase in temperature
Decrease pH (more acidic)
Increase CO₂
Increase in 2,3-DPG (produced in erythrocytes in glycolysis, increases when Hb O₂ is low)
71
Oxygen delivery to systemic tissues
Rate of delivery \> rate of O₂ consumption (gives safety margin)
Oxygen delivery = Q x CaO₂ (rate of flow x oxygen content of arterial blood)
72
Hypoxaemia (hypoxic hypoxia)
Low arterial PO₂, so decreased saturation of Hb, decreased O₂ content
Caused by
- decreased inspired PO₂
- hypoventilation
- impaired diffusion
- V/Q inequality, shunt
Decreased arterial PO₂, decreased venous PO₂, cyanosis possible
73
Ischaemic hypoxia
Decreased perfusion of tissues (inadequate blood flow)
Caused by
- cardiac failure
- arterial or venous obstruction
Normal arterial PO₂, decreased venous PO₂, cyanosis possible
74
Anaemic hypoxia
Decreased O₂ binding capacity
Caused by
- anaemia
- abnormal Hb eg in CO poisoning
Normal arterial PO₂, decreased venous PO₂, cyanosis unlikely
75
Histotoxic hypoxia
Impairment of respiratory enzymes
Caused by
- cyanide poisoning
Normal PO₂, increased venous PO₂, cyanosis unlikely
76
Signs and symptoms of acute hypoxia
SIGNS:
- ataxia (loss of motor control)
- convulsions
- confusion
- tachycardia
- sweating
- coma
SYMPTOMS:
- euphoria
- fatigue
- headaches
- light-headedness
- tunnel vision
- anorexia
- irritability
77
Carriage of CO₂ in the blood - in solution
PCO₂ relatively low (40mmHg in alveoli)
BUT 20 x more soluble than O₂
-\> at PCO₂ of 40mmHg, 100mls blood has 2.4 ml of CO₂ in solution
78
Carriage of CO₂ in the blood - as bicarbonate
CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻
First stage is SLOW, accelerated by carbonic anhydrase, which is only found in RBCs so reaction mainly occurs here.
CO₂ in plasma diffuses to RBCs, becomes H⁺ + HCO₃⁻
H⁺ causes Hb to release O₂, which diffuses out to plasma, HCO₃⁻ diffuses straight to plasma
79
Effects of Haemoglobin buffering H⁺
Hb binds to H⁺, so buffers it, causing:
- stops free [H⁺] rising too much in blood
- decreases affinity of Hb for O₂, so O₂ is released where CO₂ is present, at site of respiration
80
Carriage of CO₂ in the blood - as carbamino compounds
Protein with NH₂ group + CO₂ ↔ Protein with COO⁻ group + H⁺
Mainly in RBCs, where Hb provides rich source of NH₂ groups via 4 polypeptide chains with amines
Hb buffers H⁺
81
Haldone effect
Increasing PO₂ decreases the amount of CO₂ carried in blood
But much more CO₂ is in blood than O₂, as it has many different ways of being carried and is more soluble
82
Hypercapnia signs and symptoms
- vasodilatation
- bounding pulse
- papilloedema (swelling of optic disc in eye)
- flapping tremor
- depressed conscious level
- respiratory acidosis and decreased cardiac contractility
83
Acid base implications of CO₂
CO₂ is a volatile acid, becomes H⁺
Eliminated by ventilation
Changes in PaCO₂ alter pH of blood
Blood is slightly alkaline, especially in veins
84
Respiratory acidosis
More H⁺ due to more CO₂, so more HCO₃⁻ to compensate from kidney (-\>long term changes in pH)
Caused by alveolar hypoventilation or chronic condition eg asthma, COPD, pneumonia, sleep apnea
85
Acidosis symptoms
- headache, sleepiness, confusion, loss of consciousness, coma
- seizures, weakness
- diarrhoea
- shortness of breath, coughing
- arrythmia, increased heart rate
- nausea, vomiting
86
Generation of respiratory rhythym
Inspiratory neurones stimulate motorneurones of phrenic (diaphragm, C3-C5) and external intercostal (T1-T11), causing contraction of inspiratory muscles
Ventilation is regulated intrinsically by O₂, CO₂ and pH in lungs, overriding voluntary control
87
Brain controlling respiration
Medulla is centre for basic control of respiration, produces respiratory drive
Pons regulates the medulla- pneumotaxic centre and apneustic centre
Pneumotaxic centre is stimulated by apneustic centre and outflow from inspiratory neurones
Apneustic centre is tonic stimulation of inspiration, inhibited by pulmonary stretch receptors and by pneumotaxic centre
-\> Together they facilitate transition between inspiration and expiration (inspiration inhibits inspiratory drive)
88
Central hypoventilation syndrome, Ondine's curse
Respiratory control centre stops working, so when unconscious there is no respiratory drive and no breathing
Requires ventilator before sleeping
89
Central chemoreceptors (medulla)
Beneath ventral surface of medulla, near exit of cranial nerves 9 and 10 (glossopharyngeal and vagus)
Anatomically separate from medullary respiratory centre
Minute to minute control of ventilation
Surrounded by brain extracellular fluid
Respond to [H⁺] in CSF Blood brain barrier protects, as H⁺ cannot cross, CO₂ can
CO₂ becomes H⁺ and bicarbonate in CSF
-\> Increased H⁺ increases ventilation drive
90
Peripheral chemoreceptors (carotid bodies and aortic bodies)
- Carotid bodies at bifurcation of common carotid arteries (where blood goes to brain) - most important
- Aortic bodies (where blood goes to system)
Respond to decreased arterial PO₂ and pH, and responds to increased arterial PCO₂
Without these receptors, lose ventilatory response to hypoxia
High blood flow here, small arterial-venous O₂ difference in spite of high metabolic rate
Carotid body info via glossopharyngeal to medulla Aortic body info via vagus to medulla
91
Effects of arterial PO₂ on ventilation
Normal resting level of O₂ sits of plateau, so small changes will not bring about a change in ventilation
Normal resting level of CO₂ on steep part of curve, so small changes in CO₂ bring a marked change in ventilation
Therefore minute to minute ventilation mainly driven by CO₂ and not O₂
92
Central chemoreceptors
In ventral medulla
Responds to changes in pH
Insensitive to hypoxia
93
Peripheral chemoreceptors
In aortic and carotid bodies
Responds to changes in arterial PO₂, pH and PCO₂
94
Lung stretch receptors
Within smooth muscle of walls of airways
Lung inflation increases frequency of impulses in vagal afferents, increasing expiratory time and decreasing breathing rate
95
Irritant receptors
Between airway epithelial cells
Smoke, dust, cold air etc trigger vagal afferents
Causes bronchoconstriction, increasing breathing frequency
96
Type I respiratory failure
Hypoxic hypoxia (hypoxaemia), without hypercapnia = Lung failure
Caused by
- decreased inspired PO₂
- shunt
- V/Q mismatch
- impaired diffusion
eg altitude, congenital cyanotic disease, fibrosis, pulmonary embolus
97
Type II respiratory failure
Hypoxaemia AND hypercapnia = Pump failure
Caused by
- CNS or PNS disease
- chest wall or upper airway problems
eg stroke, opiate overdose, myasthenia gravis, burns, laryngospasm, oedema
98
Normal physiological values - Respiration rate, O₂ saturation, PaO₂, PaCO₂
Respiration rate - 12-20pm
O₂ saturation - 96-100%
PaO₂ - 80-105 mmHg
PaCO₂ - 35-45 mmHg
99
Bronchopneumonia
Areas of patchy tan-yellow consolidation (dense material)
Remaining lung shows pulmonary congestion, dark red
Alveoli filled with neutrophilic exudate
TYPICAL BACTERIA
- Staph aureus, Klebsiella, E coli, Pseudomonas
CXR
- diffuse, patchy shadowing
- loss of sharp borders; blunted costophrenic angle and heart borders
100
Lobar Pneumonia
Consolidation of entire lobe
TYPICAL BACTERIA
- Streptococcus pneumoniae (95%)
CXR
- white patch of increased opacity bordering fissures, better defined than in bronchopneumonia
101
Viral Pneumonia
Interstitial lymphocytic inflitrates, no alveolar exudate
CAUSES - influenza A and B, parainfluenza, adenovirus, metapneumovirus
- respiratory syncitial virus (in children)
- cytomegalovirus (if immunocompromised)
102
Sinusitis
CAUSES
- mainly viral - Streptococcus pneumoniae, Haemophilius influenzae, Moraxella catarrhalis
TREATMENT
- antibiotics only in severe or prolonged infections more than 5 days SIGNS
- facial view X ray shows fluid, meniscus in sinus (but rarely X ray)
103
Asthma
Starts in childhood normally, 1/10 children, 1/20 adults
Increased risk with family history and allergies
Typical triad of asthma, eczema and allergic rhinitis
Histology - see submucosa widened by smooth muscle hypertrophy, oedema, inflammation (mainly eosinophils)
104
COPD
Persistent productive cough for more than 3 months over 2 years
5% worldwide population
SMOKING
SEE
- black carbon deposits in lung
- inflammation in lung
\> bronchitis (inflammation and narrowing of small airways
\> more chronic inflammatory cells in submucosa, neutrophils and macrophages
\> breakdown of lung issue (emphysema), loss of alveolar walls
Damage is cumulative and permanent
105
Lung cancer
Carcinoma, from epithelial cells
Histology - nests of polygonal cells with pink cytoplasm, distinct cell borders
Two classes, small-cell and non-small-cell lung carcinoma, important for predicting outcome
CXR
- mass
- widening of mediastinum
- collapse (atelectasis)
- consolidation
- pleural effusion
106
Pharyngitis
VIRAL
- 80%
- adenovirus / infectious mononucleiosis / common cold
BACTERIAL
- 20%
- group A beta haemolytic streptococcus / Haemolytic influenza / Streptococcus pneumoniae
107
Influenza
Type A most common, also B and C
RNA viruses
Seasonal variation
Pandemics (eg bird/swine flu)
CONTAGIOUS - airbourne, direct contact, surface contact
108
LRTI
Lower Respiratory Tract Infection
Any infection of respiratory tract from vocal chords downwards
Should be sterile here!
Colonisers are often from URT, eg Haemophilius influenzae, Streptococcus pneumoniae
Antibiotic therapy will affect URT also
109
LRTI sequence of events
Abnormal flora in LRT
- \> paralysis of cilia
- \> excessive volume or viscosity of mucus
- \> failure to protect LRT
- \> failure to cough up debris from larger airways
- \> loss of swallow reflex
110
Chronic bronchitis
Antibiotic therapy if two of
- increased breathlessness
- increased sputum volume
- increased sputum purulence (mucky/different)
-----\> problems with diagnosis, normal exacerbations of COPD will cause (first two) even without infection, purulence is main indicator
TREATMENT
- 1st - Beta lactam - amoxicillin, acts on cell wall
- 2nd - tetracycline, acts on ribosomes
- 3rd - macrolide, acts on ribosomes
111
Community acquired pneumonia
CAP
More common in winter
2 x more in men than women
More in elderly
112
Symptoms of CAP
- acute LRTI symptoms (cough and one other)
- new focal chest signs on examination
- one or more systemic features (sweating, fever, shivers, aches and pains, temp above 38°C
- no other explanation for illness
--\> treat with antibiotics
113
CRB score for mortality risk assessment in CAP
One point for each of:
Confusion
Raised resp rate (30+pm)
Blood pressure low (less than 90/60)
aged 65+
0- low risk, home treatment
1/2- moderate, consider hospital referral
3+ -high risk, urgent hospital admission
114
Main pathogens causing CAP
In GP
- Streptococcus pneumoniae
- Haemophilius influenzae
- Viruses
In hospital
- more atypical bugs, chlamydophila pneumoniae and mycoplasmia pneumoniae
115
Streptococcus pneumoniae (PNEUMOCOCCUS) causing CAP
Gram +ve diplococcus
Colonises URT in 10% adults
Alpha haemolytic - produces enzymes that haemolyse RBCs by producing hydrogen peroxide -\> green
Can be commensal, virulence potential
More than 90 recognised serotypes
Encapsulated -\> lobar and bronchopneumonia
Vaccines in childhood and the elderly (eg PVC 13 covers 13 serotypes)
116
Haemophilius influenzae causing CAP
Gram -ve
Capsulated and uncapsulated strains
Mainly in lung disease and smokers
20% B lactamase positive, so make enzyme that degrade B lactam antibiotics, the usual 1st line treatment
117
Atypical pneumonia causing CAP
Atypical pathogens
- mycoplasma pneumoniae
- legionella pneumophilia
- chlamydophilia pneumoniae
- chlamydophilia psittaci
Insidious onset usually, comes on slowly with few symptoms
Classically; non-productive cough, fever, headache, chest radiograph more abnormal than clinical assessment suggests
Often sub-clinical, many cases go undiagnosed
118
Mycoplasma pneumoniae causing atypical CAP
No peptidoglycan cell wall
Resistant to B lactam antibiotics
Primary cause of atypical pneumonia (~15%)
119
Legionella pneumophilia causing atypical CAP
= Legionnaire's disease
Lives and multiplies inside macrophages, so hard to target
Often from aircon units/after trip abroad
Causes severe pneumonia, high mortality rate
120
Chlamydophilia pneumoniae and Chlamydophilia psittaci causing atypical CAP
Obligate intracellular parasite (only in cell)
Chlamydophilia pneumoniae usually self-limiting and mild
Chlamydophilia psittaci can cause severe pneumonia, associated with bird contact
121
General investigations on hospital admission for CAP
Full history and examination
Oxygen saturations, arterial blood gases, bp, temp
CXR
Urea and electrolytes (added to CRB, now CURB)
CRP
Full blood count
Liver function test
122
Low severity CAP treat with:
5 day course single antibiotic, amoxicillin usually
Extend course if symptoms not improved in 3 days
123
Moderate severity CAP treat with:
7-10 day course of antibiotics
Dual treatment with amoxicillin and macrolide
124
High severity CAP treat with:
7-10 day course of antibiotics
Dual treatment with B lactamase stable B lactam and macrolide
Need broader therapy if hospital acquired! (atypical)
125
Lung abscess
Pus, mainly neutrophils
Caused by
- aspiration of GI content into lungs
- periodontal disease
- septic emboli
- bacteraemias
To treat
- drain abscess
- CXR and CT
- blood cultures
- culture aspiration fluid
- antibiotics 4-6 weeks
126
Cystic Fibrosis newborn screening
At 5 days old, heel-prick test in home
Confirm with sweat test around 2 months old, and DNA testing
127
Complications in baby with CF
Pancreatic insufficiency - faecal elastase low
Pulmonary infection
- flexible fibreoptic bronchoscopy used if recurrent cough - avoided as is invasive, requires general anaesthetic
Fat soluble vitamin deficiency - yearly blood tests to check, low E -\> anaemia, low A and D -\> vision and bone problems long term, low clotting factors
128
Additional complications in adults
CF diabetes
CF bone disease
Fertility/pregnancy complications
Genetic counselling needed, psychological problems
GI/liver problems
129
What is Cystic Fibrosis?
Affects exocrine glands of liver, lungs, pancreas, intestines
-\> progressive disability due to multisystem failure
Autosomal recessive inheritance, mutations in CFTR on chromosome 7, leading to defective ion transport
130
Symptoms / signs of CF in an infant
- Meconium ileus (apparent in newborns) = acute intestinal obstruction, bilious vomiting, abdominal distension ----\> requires medical and surgical assistance: enema, laporotomy, resection
- Failure to thrive
- Thin, fretful, feeding doesn't satisfy
- Steatorrhoea
- Persistent moist cough
- Clubbing
131
Symptoms / signs of CF in an older child
- Loose, smelly stool
- Recurrent chest infections, pneumonia
- Chest deformity (Harrison's sign, chest falling in)
- Clubbing
132
Symptoms / signs of CF in an adult
May be classical presentation, or no features
- Pancreatitis
- Sinusitis, recurrent
- Male infertility (absence of vas deferens, azoospermia,(can still father children if sperm collected from testes))
If non classical, lower degree of morbidity and treatment burden
133
Management of cystic fibrosis
- Hospital visits every 6-8 weeks, with large multidisciplinary team
- Prophylactic antibiotics
- Fat soluble vitamins (ADEK)
- Twice daily physiotherapy
- Inhalers, nebulisers
- Mucolytics
- Steroids
- Pulmonary lobectomy in established and severe bronchiectasis, persistent infection
134
Improved survival rate of CF in current age due to:
- Nebulisers to assist airway clearance
- Nebulised and IV antibiotics
- Avoidance of BMI less than 19
- Physiotherapy
135
Genetics of CF
- 1/25 carry faulty CFTR gene in UK
- 1/4 chance of passing on if both parents carriers
Different ways of non-functioning CFTR gene:
I - defective protein production
II - misfolded protein, eg ΔF508 (91%)
III - non-regulated protein, eg G551D
IV - not conducted, eg R117H
136
Pathology of intestine in CF
- Meconium ileus - failure of newborn infant to pass meconium, causing plugging of internal ileum
- Distal Intestinal Obstructive Syndrome (DIOS)
- Constipation
- Rectal prolapse, volvulus, intussusception, atresia
No villi or microvilli in ileum, many crypts secreting mucus in colon
Decreased hydration of tube
- 1) ion transport defect
- 2) different properties of mucus, stickier, more acidic
- 3) acid affects microbiota, so abnormal flora in intestine
137
Pathology of pancreas in CF
Mucus accumulates in small ducts
- \> flattening and atrophy of epithelia
- \> duct plugging and obstruction
- \> dilatation of ducts and acini
- \> fibrosis
- \> exocrine pancreas replaced by adipose tissue, so islets of langerhans in wrong environment, develop CF diabetes
138
Pathology of lung and URT in CF
Failure of lung defence mechanisms
- \> persistent bacterial infections, excessive inflammation, airway destruction
- \> bronchiectasis
Mucus plugged airways - due to goblet cell hyperplasia and disrupted function of cilia
139
Pathology of liver in CF
Biliary duct epithelial cells affected, not hepatocytes
- plugging of intrahepatic bile ducts by thick bile
- chronic inflammation and fibrosis
- hepatomegaly
- focal biliary cirrhosis
- multilobar cirrhosis
140
Other CF pathologies
Sinusitis
Nasal polyps
Salty sweat
Congenital bilateral absence of vas deferens
Osteoporosis
Rheumatic disease
Clubbing of distal phalanges
141
Chloride movements drive salt and water secretion (CFTR1)
Cystic Fibrosis Transmembrane Conuctance Regulator
- 2 membrane-spanning domains
- 2 nucleotide-binding domains (ATP needed)
- 1 regulatory domain (PKA, requires phosphorylation)
142
Normal CFTR action
CFTR is Cl⁻ channel in apical membrane
1) Cl⁻ travels into cell
2) Causes water and Na⁺ to follow paracellularly into lumen
3) Cl⁻ moves through cell to CFTR
3) 2 nucleotide binding domains receive ATP, cause 2 membrane spanning domains to come together, making a channel
4) Cl⁻ out of cell into lumen
143
Faulty CFTR action
Cl⁻ can travel into cell as normal
But faulty CFTR means cannot exit cell
Therefore no Na⁺ or H₂O out
144
ΔF508
Class II mutation
Deletion in F508
91% of CFTR mutations causing CF
CFTR protein is made but not transported to golgi or apical membrane
145
G551D
Class III mutation
6% of CFTR mutations causing CF
Protein is made and delivered to apical surface, but behaves abnormally - gate doesn't open often enough, though pathway for ion movement is normal
146
Therapy pathways for CF
Current therapies
- Airway clearance bronchodilators, mucolytics
- Antibiotics
- Anti-inflammatory agents
- Lung transplant (at bronchiectasis stage)
New therapies (target earlier in pathogenesis pathway)
- Gene therapy
- CFTR potentiators and correctors
- CFTR bypass therapy (other way for chloride to leave cell)
147
Characteristics of asthma
- wheeze
- cough
- outflow obstruction
- chest tightness
- dyspnoea
- airway hyper-responsiveness
- inflammation of lungs
148
Triggers of asthma
- respiratory infections
- exercise/breathing cold air
- exposure to allergens (pollen, moulds, dust mites, pollution, pets, tobacco smoke)
149
Prevalence of asthma
IgE levels genetically influenced, 50% more asthma in black people
Higher in city dwellers
150
Pathology of allergens triggering asthma (Pathology 1) - ALLERGENS
Allergens trigger T cells
- \> generate B-cell activating cytokines
- \> IgE production
- \> induces expression of IgE receptors (Fc) on mast cells and macrophages
151
Pathology of acute phase in asthma (Pathology 2) - IgE RECEPTORS EXPRESSED
- \> mediators released from macrophages/mast cells (eg histamine, leukotrines, cytokines, neurokinins, platelet activating factor, prostaglandins
- \> promote bronchoconstriction
- \> acute asthma attack
- \> attracts T cells, neutrophils, platelets, monocytes, which release more spasmogens and inflammogens
- \> exacerbates bronchoconstriction and triggers inflammation
152
Pathology of late phase in asthma (Pathology 3) - BRONCHOCONSTRICTION AND INFLAMMATION
- \> progressive inflammation
- \> influx of TH2 lymphocytes
- \> activation of eosinophils releasing toxic proteins
- \> PGE₂ from smooth muscle increases permeability of blood vessels
- \> oedema
- \> damage and loss of epithelium
- \> bronchial hyperactivity, increased irritant receptor accessibility
- \> subepithelial cell fibrosis
- \> hypertrophy and hyperplasia of SMCs
153
Asthma drugs - β₂ agonists - effects and mechanisms
Bronchodilators
- \> bronchodilatation
- \> inhibits release of histamine and other inflammatory mediators
- \> reduce vascular permeability and mucosal oedema
Mechanism
- activates β₂ adrenoreceptor
- increases intracellular cAMP
- activates K⁺ channel
- activates Na⁺/K⁺ ATPase
- decreases Ca²⁺ dependent coupling of actin and myosin
-\> inhibits cholinergic transmission, smooth muscle relaxation
154
Asthma drugs - β₂ agonists - drugs
Short acting, use as needed:
Salbutamol
Terbutaline
Longer acting, use twice daily if chronic asthma where glucocorticoid therapy inadequate:
Salmeterol
Formoterol
Non-selective β agonists, IV, in severe asthma:
Isoprenaline
Adrenaline
155
Asthma drugs - Xanthine drugs
Bronchodilators
Used in addition to steroids in patients non-responsive to β₂ agonists, in acute severe asthma
Mechanism unclear
Theophylline
Aminophyline
Very narrow therapeutic window - careful!
Theophylline is metabolised by liver, half life dependent on liver function
156
Asthma drugs - muscarinic receptor antagonists
Bronchodilators
Inhibit M3 receptors, so less smooth muscle contraction and secretion
May also inhibit M2 so reduced effectiveness
Inhibit mucus secretion
Used as adjunct to β₂ agonists or to relieve bronchospasm
Ipratropium bromide
Tiotropium
157
Asthma drugs - cysteinyl leukotrine antagonists
Anti-inflammatory, acting on 5-lipo-oxygenase pathway
Zileutin inhibits arachidonic acid -\> leukotrines
Montelukast inhibits leukotrines effects (so decreases bronchoconstriction, oedema, inflammation, chemoattraction)
158
Asthma drugs - glucocorticoids
Anti-inflammatory
Immunosuppressive
Decreases IL3 synthesis, decreases cytokine production
- so decreases microvascular permeability
- so relaxes bronchial muscle by increasing β₂ adrenoreceptor levels, increasing G protein expression
Inhaled glucocorticoids are first line where symptoms persist despite 2x daily inhaler
159
Asthma drugs - glucocorticoids - drugs
Inhaled:
Fluticasone
Budesonide
Beclometasone dipropionate (BDP)
Systemic, for severe asthma:
Prednisolone
Prednisone - needs to be converted in liver to active form, so good in pregnancy
Hydrocortisone
160
Asthma drugs - other anti-inflammatory drugs
Cromoglicate
Nedocromil
161
Asthma drugs - histamine receptor antagonists
= antihistamines
Fexofenadine
Cetrizine
162
Management of asthma
1) Mild disease - control with short acting bronchodilator as needed
2) If needed more than 1x daily - add inhaled glucocorticoid
3) If still uncontrolled - add longer acting bronchodilator
4) If still uncontrolled - go to maximum dose of glucocorticoid and add theophylline/montelukast 5) If still uncontrolled - go to oral glucocorticoid
163
Status asthmaticus
= severe acute asthma
Needs emergent hospitalisation, treat with oxygen, nebulised salbutamol, IV hydrocortisone, IV salbutamol
164
OSHIT! Asthma attack
Oxygen
Salbutamol
Hydrocortisone
Ipratropium
Theophylline
(! Magnesium)
165
Allergic emergency - anaphylaxis
= food allergy
Treat with adrenaline, oxygen, anti-histamine, hydrocortisone
166
Allergic emergency - angio-oedema
= intermittent focal swelling of skin
Aspirin worsens
Treat with leukotriene antagonists
167
COPD symptom progression
Morning cough in winter -\> chronic cough -\> URTI/bronchitis -\> progressive breathlessness -\> pulmonary hypertension, heart failure
168
COPD pathogenesis
- small airway fibrosis, bronchitis
- destruction of alveoli/elastic fibres = emphysema, promoted by protease release due to inflammatory response
---\> impaired gas transfer and chronic inflammation
169
COPD treatment
STOP SMOKING
Immunise against infection
Long acting bronchodilators - modest benefit, no effect on inflammation (steroids ineffective)
Long term oxygen therapy
170
COPD cough
Protective reflex to remove foreign material/secretions
Productive, removes sputum from lungs. If dry cough, commonly seen if on ACE inhibitors.
Cough suppression only if a dry painful cough- anti-tussives
171
COPD drugs - Anti-tussives
OPIOIDS: analgesics act on cough centre in brain (Codeine, dextromethorphan, pholcodine, morphine)
DEMULCENTS: for cough originating above larynx, forms protective coating over irritated pharyngeal mucosa, syrups of lozenges (natural)
LOCAL ANAESTHETICS: inhibit cough reflex, only used eg before bronchoscopy
172
COPD drugs - Expectorants
Decrease bronchial secretion viscosity, so easier to cough out.
Adequate hydration more important!
Guafenesin, iodides (eg potassium iodide, iodinated glycerol, to break up bronchial secretions)
173
COPD drugs - Decongestants
α receptor agonists
- \> vasoconstriction of nasal blood vessels
- \> reduce nasal mucosa volume
- \> open airways
Used topically for short term relief
Short acting
- oxymetazoline
- hydrochloride
Long acting
- pseudoephedrine
174
Symptoms of tuberculosis
Chronic cough
Sputum production
Appetite loss
Weight loss
Fever
Night sweats
Haemoptysis
175
Mycobacterium tuberculosis
Gram +ve
Obligatory aerobe
Slow growing
-\> intracellular infection
176
Epidemiology of tuberculosis
1.7 billion affected, 1.6 million deaths annually
But infection≠disease (presence of mycobacteria≠clinical manifestation)
177
Risk factors for tuberculosis
HOST FACTORS
Proximity, duration of contact
Age
Immune status, malnutrition, diabetes
ENVIRONMENTAL FACTORS
Crowding, poor ventilation
Smoking, alcohol, occupation
178
Primary tuberculosis: 0-3 weeks
Asymptomatic
or
Fever, malaise, tiny fibrocalcific nodule at site of infection
Bacteria enter macrophages by endocytosis
- \> prevent phagosome-lysosome fusion
- \> inhibit lysosome acidification
- \> lipopolysaccharide inhibits IFN-γ
179
Primary tuberculosis: 4-6 weeks
- TH1 response activates macrophages to become bactericidal
- TH1 release IFN-γ, stimulating macrophages to form phagolysosome complex to contain infection
- TH1 stimulate formation of granulomas by triggering macrophages -\> epitheloid histiocytes
180
Granuloma
In tuberculosis
Mycobacterium tuberculosis and necrotic infected macrophages are at the core
T and B cells surround
Fibrous border at outside to prevent rupture
181
TB progression
Primary infection -\> Primary complex -\>
1) Healed lesion (scar)
2) Progressive primary TB -\> miliary TB (haematogenous spread)
3) Latent lesions - - -\> if reactivated become secondary TB -\> miliary TB - - -\> cavitary TB if immune system compromised, can NOW be spread via cough etc
182
Miliary TB
Every organ in body will have nodules- kidney, testes, liver, spleen, lymph nodes etc
183
Epidemiology of asthma
Earlier onset indicative of more severe asthma
Exposure to smoking/pollutants during early years is significant (some countries higher risks)
184
Early/late/persistent asthma
TRANSIENT EARLY WHEEZERS
- peak age 0-3 years, usually with viral infection
- gone by age 6
NON-ATOPIC WHEEZERS
- age 4-5
IgE ASSOCIATED WHEEZE
- increasing wheeze prevalence throughout early years
185
Hygiene hypothesis
Decreasing exposure to microbes increases hygiene, increases allergies and asthma
Good to have infections early in life!
Upregulates TH1, downregulates TH2
186
Small cell lung carcinoma
12-15% cases
Aggressive - 5% 5 year survival
Usually bilateral, so inoperable
187
Non-small cell lung carcinoma
80-85% cases
Good prognosis - 75% 5 year survival
Presents earlier, so can be operable
188
Risk factors for lung cancer
Smoking
Age - 45-75 mainly
Occupational factors
Genetic (influence)
Diet - dietary fat increases chemically induced pulmonary tumours
Prior respiratory disease - asthma, emphysema etc - as chronic immune stimulation leads to random pro-oncogenic mutations
Gender - more common in men
Socioeconomic class - more in lower
189
Embryology of lower respiratory tract
Endoderm - ventral growth from foregut to -\> respiratory epithelium
Mesoderm -\> lung tissue (parenchyma), muscular diaphragm, pleural cavities
190
Embryonic period - week 4-8
Future trachea evaginates from foregut -\> oesophagus and trachea
Lung buds become lung shaped and primary bronchi form
191
Tracheoesophageal fistula
Can be blind-ended oesophagus, communication between, etc
Baby vomits milk, risk of aspiration
Foetus cannot practise breathing or swallowing, fluid around baby is a marker
192
Pseudoglandular period - week 5-17
Conducting airways branch
Epithelia become tall columnar and cuboidal
By week 8, all segmental bronchi formed
193
Canalicular period - week 16-26
Epithelia differentiate so respiratory bronchioles formed - distinction between gas exchange vs conducting airways
Canalisation of lung parenchyma by capillaries
194
Surfactant deficiency
= Infant respiratory distress syndrome
Airsacs collapse on expiration as increased surface tension
So more energy required for breathing
Need to give exogenous surfactant to reduce mortality and pulmonary air leaks (pneumothorax)
195
Saccular period - week 24-38
Terminal sacs form (primitive alveoli), associated with blood vessels
Cuboidal cells flatten, become type 1 pneumocytes
Vascular tree increases in length and diameter
Type II pneumocytes produce surfactant
196
Alveolar period - week 36-8years
Terminal saccules replaced by mature alveoli
Only 16% alveolar cells present at birth, process continues
197
Pleural cavities - inc congenital diaphragmatic hernia
Derived from mesoderm
Single body space separated into three cavities - pleural, pericardial, peritoneal
Diaphragm develops via pleuroperitoneal separation
If incorrectly forms, congenital diaphragmatic hernia - gut contents pushes up into chest, baby can't breathe properly
198
Embryology of nasal cavity
Formed from frontonasal prominence
Nasal placode appears at WEEK 4
Cavity is formed from 5 facial prominences
- 2 medial
- 2 lateral
- 1 frontal
- -\> cleft/lip palate if incomplete as face forms from side to midline
199
Embryology of larynx
Pharyngeal arches from
- the core of mesoderm -\> cartilage, muscle, connective tissue
- inner endoderm -\> epithelial lining 4-6 pharyngeal arches make larynx
Each pharyngeal arch is associated with a specific cranial nerve (10 for larynx)
--\> if orifice doesn't open, fatal, miscarriage at 12 weeks as lung needs to develop
200
Spirometer graph
