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Flashcards in Systems 2 - Respiratory Deck (200):
1

Respiration definition

-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

Trachea structural features - Cartilage

Supporting C circles of hyaline cartilage

Provide structure

Incomplete ring, so bolus can pass through oesophagus in swallowing

3

Trachea structural features - Cells

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

Bronchioles structural features

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

Alveoli structural features

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

Cells in alveoli

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

Functions of the airway

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

Measurement of Functional Residual Capacity

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

Residual volume

Residual Volume = Functional residual capacity - End residual volume

10

Anatomical dead space

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

Physiological dead space

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

Estimated dead space (ml)

2.2 x body weight (kg)

Usually approx 165ml, 1/3 of tidal volume

13

Minute volume

Volume of gas breathed in or out per minute

Minute volume = Tidal volume x frequency

14

Alveolar ventilation

(Vt-Vd) x frequency

15

Fraction of alveolar CO₂

Fraction of alveolar CO₂ ∝ Rate of production of CO₂ / Alveolar ventilation

16

Correcting volume for different conditions

V₂ = V₁ x T₂/T₁ x P₁/P₂

To correct for pressure and temperature

17

Pressures in lung lining

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

Boyle's law

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

Process of inspiration

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

Process of expiration

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

Pneumothorax

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

Work of breathing

30% for airway resistance

65% for compliance (elasticity of lung)

5% functional resistance

23

Airway resistance

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

Pouiselle's law, airway resistance

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

A image thumb