RS Lecture 11 and 12 - Lung Infection and Lung Mechanics

Question 1

What are the mechanical defense mechanisms of the respiratory tract against infections?

Answer 1

URT filtration, mucociliary clearance, cough, surfactant, epithelial barrier

Question 2

What are the local defense mechanisms of the respiratory tract against infections?

Answer 2

BALT -> IS within resp tract that samples Ag we inhale and produce Ab to neutralise it; sIgA, lysozyme, transferrin, antiproteinases, alveolar macrophages

Question 3

What are the systemic defense mechanisms of the respiratory tract against infections?

Answer 3

Polymorphonuclear leucocytes, complement, immunoglobulins

Question 4

Where do ciliated epithelium line?

Answer 4

All airways up to respiratory bronchioles, knitted together with tight junctions

Question 5

What surrounds the cilia?

Answer 5

Periciliary fluid which is watery -> mucus floats on top of cilia and is more sticky and gel-like

Question 6

What happens when an infectious particle is breathed in?

Answer 6

It sticks to the mucus on the top and the beating of underlying cilia drive mucus up to back of throat where it is swallowed/coughed up

Question 7

How often does each cilium beat?

Answer 7

15 x per second -> to a metachromal rhythm

Question 8

How do the cilia beat the mucus in one direction?

Answer 8

Coordinated -> backward movement is different to forward movement -> downward stroke engages with mucus to push it forward, then at the bottom of forward movement, cilium withdraws in curved fashion, withdrawn within periciliary fluid back to start to repeat movement

Question 9

How are the cilia specialised to engage with the mucus?

Answer 9

Little claws on their tips

Question 10

What is the structure of a cilia?

Answer 10

9+2 pattern -> 9 pairs of microtubule around outside which have dynein arms

Question 11

What do the dynein arms contain?

Answer 11

ATPase, which provides energy for microtubules in the cilium to move up and down each other to make the cilia bend -> central microtubules used as an axis

Question 12

What are the 2 most common acquired defects of the mucociliary system?

Answer 12

Cigarette smoking and viral infection

Question 13

What happens when a virus invades you airways?

Answer 13

Cilia are destroyed, cold-like symptoms, tight junctions fall apart -> mucus become yellow-green colour

Question 14

Why does mucus become yellow-green when infected?

Answer 14

Bacterial infection has capitalised on the weakness of resp epithelium brought about by virus

Question 15

What happens after the virus has been cleared?

Answer 15

Cilia need time to regrow, with mucociliary system disabled for around 6wks, but cilia can grow back as compound cilia (useless)

Question 16

What are some respiratory infection syndromes?

Answer 16

Acute (overwhelming) - due to very virulent bug or disorder of host defence. Recurrent-acute (slow to resolve) - bronchial, pneumonic, abnormalities in host defences present in people with recurrent acute illnesses. Daily purulent sputum only temporarily responding to AB - releasing yellow/green phlegm on a daily basis is also unusual, could be abnormality of host defences

Question 17

What is dextrocardia and what does it suggest?

Answer 17

Heart pointing towards RHS, suggests there could be a ciliary abnormality -> 50% of people born without functioning cilia have dextrocardia

Question 18

Why does dextrocardia occur in those without functioning cilia?

Answer 18

Because microtubules are used to guide the cells around during embryological development

Question 19

What cilia defect can occur?

Answer 19

Dynein arm defect -> outer dynein arm isn’t present, so cilia don’t work

Question 20

What are the levels of NO in normal and people with primary ciliary dyskinesia?

Answer 20

People with PCD have less NO than normal people -> have less nasal NOs

Question 21

What are some bacteria that infect the airway?

Answer 21

Haemophilus influenzae is the most common cause of bronchitis and sinusitis

Question 22

How is Haemophilus influenzae adapted for airway infection?

Answer 22

Hair-like fimbriae that act as anchors to get the bug to attach to the epithelial surface -> once on epithelium it begins to divide and form a colony

Question 23

Where do bacteria stick onto in the airway?

Answer 23

Onto DAMAGED epithelium not where there are cilia

Question 24

What are some bacterial strategies to avoid clearance from the airways?

Answer 24

Exoproducts, Enzymes -> break down local Ig. Exoproducts, Adherence, Avoiding immune surveillance.

Question 25

How do exoproducts impair mucociliary clearance and affect WBCs?

Answer 25

Impair mucociliary clearance by slowing and disorganising ciliary beat, stimulate mucus production, affect ion transport and damage epithelium. Impair neutrophil, macrophage and lymphocyte function.

Question 26

How does adherence help bacteria avoid clearance from airways?

Answer 26

Increased by epithelial damage and tight junction separation.

Question 27

How do bacteria avoid immune surveillance in the airways?

Answer 27

Surface heterogeneity, biofilm formation, surrounding gel and endocytosis

Question 28

What are the clinical features of pneumonia?

Answer 28

Cough, sputum, fever, dyspnoea, pleural pain (pain fibres on surface of lungs, so when lung solidifies and inflammation enters periphery, stabbing pleuritic chest pain occurs), headache

Question 29

What is the most common cause of bacterial pneumonia and how is this bacteria adapted to be virulent?

Answer 29

Streptococcus pneumoniae -> has a polysaccharide capsule around it (negatively charged), so bug has difficulty binding to epithelium but makes it more virulent and is able to invade bloodstream and cause systemic invasion -> produces toxin that punches holes in cells and kills them (pneumolycin)

Question 30

What is bronchiectasis?

Answer 30

Abnormal widening of bronchi or their branches, causing risk of infection

Question 31

What is gas trapping and what causes it?

Answer 31

Inspiration requires muscles to function, and for expiration passive recoil from lung elasticity is enough, however if lung is diseased and has lost its elasticity, so as it collapses back, the airways close down and air gets trapped -> hence why people with diseased lungs have much higher residual volume

Question 32

What is the histology of bronchiectatic airways?

Answer 32

Dilated airways strung together by scar tissue, with pooling of phelgm

Question 33

What are the common complaints of patients with bronchiestasis?

Answer 33

Daily sputum production, recurrent respiratory infections, breathlessness (asthma and small airways disease), fatigue (severe tiredness and lethargy, difficulty concentrating)

Question 34

How can removing the built up phlegm help patients?

Answer 34

People do physiotherapy every day to empty lungs and by getting rid of dirty phlegm, you remove the stimulus for the neutrophils to move in, reducing the inflammation

Question 35

What are the 8 causes of bronchial sepsis?

Answer 35

Congenital, mechanical obstruction, inflammatory pneumonitis, fibrosis, postinfective, immunological, impaired mucociliary clearance, immune deficiency -> people with Marfan’s syndrome can also have it

Question 36

What is the vicious cycle of infection and inflammation and how is it caused?

Answer 36

If the infection becomes chronic then you also get chronic inflammation, which in itself can damage the body, due to impaired lung defences which the inflammation further damages lung defences causing more infection and inflammation

Question 37

What is the most important cause of the damage from inflammation?

Answer 37

Protease-antiprotease balance

Question 38

How does the protease-antiprotease balance cause damage?

Answer 38

Neutrophil enters airway and releases proteases to kill the bacteria that it phagocytosed, with a little bit of protease spilling during phagocytosis onto the surrounding tissues, usually anti-proteases are present in the airways to neutralise it but with chronic inflammation too many neutrophils release too much proteases, so it overwhelms the antiproteases, so free proteases sit in yellow-green sputum and cause damage

Question 39

What do proteases do?

Answer 39

Break down the elastin, digesting structure of bronchial wall, eats away at the epithelial surface causing damage

Question 40

Whats the difference between normal, obstructive and restrictive pulmonary diseases?

Answer 40

Obstructive has bigger RV due to trapped air or due increased resistance, so is more difficult to move air (decreased radius due to mucus); restrictive has smaller RV due to chest wall not being able to expand. TLC is bigger in obstructive, smaller in restrictive. VC decreases in both obstructive and restrictive.

Question 41

What are the chronic and acute causes of obstructive PD?

Answer 41

Chronic: COPD, emphysema, bronchitis. Acute: asthma

Question 42

What are the pulmonary and extrapulmonary causes of restrictive PD?

Answer 42

Pulm: Lung fibrosis, interstitial lung disease. Extrapulm: obesity, neuromuscular disease

Question 43

What is the mechanism of ventilation?

Answer 43

Small change in pressure gives a relatively large change in volume -> middle of curve. Huge amount of energy needed to change the same amount of volume -> at the ends

Question 44

How do the lungs interact at different points of the graph?

Answer 44

Tending towards y-axis can be done steadily with recoil force or actively (expiration) -> NO NET AIRFLOW right: just after tidal inspiration; left: apply just a little bit of expiratory force; middle: functional residual capacity

Question 45

How much energy is needed for tidal inspiration and expiration?

Answer 45

Tidal inspiration needs muscular effort, so energy; but tidal expiration is a passive process

Question 46

How do the mechanics of ventilation change for restrictive and obstructive PD?

Answer 46

Restrictive: VC is smaller, FRC is lower, sigmoid shape is flattened, so to reach either ends even greater pressure is needed. Obstructive: Curves are narrower, flatter and is pushed higher -> more compliant, so bigger forces = bigger changes to volume

Question 47

How does the alveolar pressure change during tidal breathing?

Answer 47

Pressure applied, so its more negative in the alveoli, so air flows in -> at the end of inspiration there is no air flow, then remove inspiratory force, so chest and lung recoil, increasing alveolar pressure, so air flows from inside to outside of lung

Question 48

What is compliance?

Answer 48

Tendency to distort under pressure -> COPD (floppy) -> compliance = change in volume/change in pressure

Question 49

What is elastance?

Answer 49

The tendency to recoil to its original volume, elastance = change in pressure/change in volume

Question 50

How does surface tension affect compliance in the lungs?

Answer 50

Filling lungs with fluid means they are more compliant -> small amount of surfactant lining the lungs and the air-water interface exhibits surface tension, but the fluid-water one doesn’t

Question 51

What is surface tension?

Answer 51

Water molecules in alveolus all interact but at the top layer, there is air one side so no mathcing force, so the top layer molecules are pulled down, causing tension across the top

Question 52

How does the shape of the alveoli affect distribution of water?

Answer 52

Distribution of water is more dense around the outside and on the inside, the water molecules are all attracted across the alveolar space to water molecules on the opposite side -> if the alveoli were too small the forces would pull alveoli together and collapse them -> surfactant ensures the collapsing pressure is lower as it spreads around the water disrupting the distribution with its phospholipids

Question 53

What is present in pulmonary surfactant?

Answer 53

80% polar phospholipids, 10% non-polar lipids, 10% protein

Question 54

What is the role of surfactant?

Answer 54

Prevents collapse of small alveoli (as there is increased surfactant in smaller ones, so overall pressure is the same), increases compliance by reducing surface tension, reduces the ‘work of breathing’

Question 55

What is resistance?

Answer 55

Resistance is inversely proportional to radius^4 -> as the airways bifurcate so rapidly, the air doesn’t really flow at the very peripherals, so resistance is very low at the peripherals of the lung

Question 56

What is conductance?

Answer 56

Resistance decreases as lung volume increases, as the airways dilate upon inspiration -> exponential decrease; conductance increases as lung volume increases -> linear relationship

Question 57

What is Poiseuille’s law?

Answer 57

Viscosity of gas (which increases resistance) = n -> radius changes resistance the greatest

Question 58

How does air flow in collapsible tubes?

Answer 58

Airway transmural pressure is a pulling force, keeping the airways open = preinspiration. Airway is patent during pre/mid/post inspiration. During forced expiration, there will be a massive increase in intrapleural pressure -> if pleural pressure exceeds the internal pressure of any collapsible tube, then airway might close making expiration difficult