Intro to Resp Medicine

• TLC - Total lung capacity = total volume of air in the lung during maximum effort of inspiration

• VC - Vital capacity = Greatest Vol of air that can be expelled from lung anger taking deep breath

• RV - Residual volume = remaining Vol of air after maximum expiration

• FRC - functional residual capacity = normal vol of air left in the lungs after expiration during normal breathing

• VT - tidal volume = Vol of air exchanged between normal insp and expiration

• IRV - inspiratory reserve volume = max amount of air that can be inspired after normal inspiration (on top of whats already inspired)

• IC - inspired capacity = max vol of air that can be inspired after normal expiration

• ERV - Expiratory reserve vol = volume of air that can be expired after natural expiration.

• Height (taller has greater volumes)

• Sex (males have greater volumes)

• Age

• Race (European>Asian)

• Respiratory diseases - this will give a reduced volume and flow rate

Volume of inspired air in which oxygen and carbon dioxide gases are not exchanged across the alveolar membrane in the respiratory tract.

It is the exchange of gas between alveoli and external evironement.

Alveolar ventilation (mL/min) = (Tidal volume (mL) - Dead Space (mL)) x Frequency of breaths (breaths/min) 

Dead space = area where no gas exchange due to lack of alveoli e.g. trachea

Respiration, olfaction, filtration, humidification, warming of air, and secretion handling

The nasal septum (medial wall)

Palantine process of Maxilla and horizontal plate of palantine bone

Cribriform plate of the ethmoid, frontal bone and sphenoid bone

Charecterised by 3 bones (conchae) - Superior, middle and inferior conchae

• The inferior concha is a separate bone while the superior and middle conchae are parts of the ethmoid bone

• The superior, middle and inferior meatus lie beneath the conchae

Perpendicular plate of ethmoid bone and Vomer

To create turbulence and warm, humidify, and slow inspired air

Increase surface area lined with pseudostratified columnar epithelium with goblet cells to secere mucus. This helps to trap dust / pathogen from the air inhaled and then get excreted.

Posterior nasal apertures connecting the nasal cavity to the nasopharynx

Cribriform plate of the ethmoid

Paranasal sinuses are hollow spaces filled in air within the bony structures of the face and they drain into nasal cavity.

• Frontal sinus - located within the frontal bone

• Ethmoidal sinus (ear cells) - located in the ethmoid bone

• Maxillary sinuses - located in the maxillary bone

• Sphenoidal sinuses - located in the sphenoid bone

• Allow skull to be lighter in weight

• Add resonance to the voice

• Absorbs shock during trauma

• Lined with mucosal cells which secrete mucus.

Sphenoidal sinuses

The paranasal sinuses drain into the nasal cavity via the meatus

• Superior meatus - drains posteior ethmoid sinus

• Middle meatus - drains maxillary, frontal and anterior ethmoid sinuses

• Inferior meatus - drains nasolacrimal duct

• Spheno-ethmoidal recess - drains sphenoid sinus

Drainage canal is higher up > Drainage is against gravity > prone to build-up of infected material.

Kiesselbach’s plexus

Trigeminal nerve (CN V)

Facial vein

Nasopharynx, oropharynx, laryngopharynx

Pharyngotympanic (Eustachian) tube

A ring of lymphoid tissue in the naso- and oropharynx

Stylopharyngeus

To propel the bolus toward the oesophagus during swallowing

The oesophagus

Has only one bone - Hyoid bone

Has 9 cartilages:

• 3x single (thyroid, cricoid & epiglottis)

• 3x paired (arytenoid, corniculate & cuneiform).

Thyroid cartilage (hyaline)

• superior thyroid notch is the laryngeal prominence = ‘adam’s apple’

• Inferior horn articulates with cricoid cartilage

• Superior horn runs towards hyoid bone but get attached to it by lateral thyroid ligaments

• Cricoid cartilage is signet ring shape

• the articular facet laterally articulates with inferior horn of thyroid.

• The tracheal ring is incomplete posteriorly = no cartilage = semicircle shape

• Thyrohyoid membrane - Attaches thyroid cartilage to hyoid bone. Runs between superior border of thyroid to inferior border of hyoid.

• Cricotracheal ligaments - attaches cricoid cartilage to superior border of 1st tracheal cartilage

Epiglottis is attached anteriorly to thyroid cartilage by thyro-epiglottic ligament.

Median cricoid ligament

• The arytenoid cartilages - (pointy bits) have apex at the top, Vocal process anteriorly and muscular process posteriorly.

  • The Vocal process attaches vocal ligaments

• Corniculates and cuneiform cartilages sits above arytenoid cartilages.

For gas exchange - to move air into the lungs to extract O2 to oxidise food which contains energy. This energy can be converted to ATP, used for bodily function.

This generates CO2 which must be exchanged out.

> Defence = filters air partilces and removes pathogens in mucus

> Metabolic = synthesise surfactants, prostaglandins and angiotensin II

> Endocrine = as above

> Haematologic = filtration of small clots, fat / cancer cells by pulmonary capillaries

> immunologic = alveolar macrophages secrete cytokines for protection

> Thermoregulatory and water elimination

> Phonation = coverts sound to speech

Assessed as the metabolic rate = how much O2 is needed at a time. Measured as O2 consumption (VO2) or CO2 production (VCO2).

• Basal metabolic rate = amount of O2 needed for basic survival ~250ml/min. In exercise it inc to ~3L/min. Daily average is ~1L/min

  
  

Metabolic rate can also be measured through CO2 production (VCO2).

RQ is the ratio of CO2 produced to O2 consumed - it indicates th type of substrate being metabolised. Used to estimate energy expenditure.

• RQ = VCO2 / VO2

RQ values (Carbs 1.0, Fats 0.7, protein 0.8, mixed diet 0.8) —> if a substrate has lower RQ = more O2 is required to metabolise it.

RQ > 1.0 = lipogenesis (excess carbs being converted to fat)

RQ < 0.7 = ketosis or starvation

• Movement of gases from environment and lung occurs through series of bifurcating airways.

• Each generation of airways (Z) is numbered (total of 23) - Trachea is Z0 > bifurcate to 2 bronchi Z1

• 1st 16 generation is known as conducting zone - no gas exchange due to thick surface.

  • Air moves by convection (bulk) in conducting zone.

• Generation 17 to 23 are transitional and respiratory zones. - the membrane gets thinner down the generation = gas exchange occurs at an increasing rate.

  • The surface area also increases beyond gen 17

The relationship between airway generation (Z) and surface area is what determines speed at which air moves through the lungs:

• Flow (cm3/sec) = Speed (cm/sec) x Area (cm2)

As we move down the airway, overall SA increases = air is spread over wider area = speed reduced.

• Z17 onwards, gas speed is determined by speed of diffusion (as opposed to convection / bulk movement in the conducting zone Z0-Z16).

Partial pressure gradients

• Gas diffuse down the gradient from high to low.

• To increase O2 flow across patient’s lung, the diffusion gradient need to be increased = increase pO2 within respiratory zones > high gradient > increase rate of diffusion.

• Can’t just increase convection!

• PB = atmospheric pressure = pressure exerted by weight of gas molecule in the atmosphere at given location. Measured in kpa

• At sea level PB is ~100kpa and this decreases with high altitude (every 5450m above sea level, PB is halved)

• Partial pressure = pressure of any particular gas (O2/CO2) which depends on no of molecule of that gas in given volume

  • Related by Dalton’s Law of PP which states total pressure is the sum of partial pressures.

  • Partial pressure = Fractional concentration of a gas in a mixture x Total pressure

Dead space is the vol of gas within the respiratory system in which gas exchange does not occur

• Anatomic dead space = present in everyone

  • It is air in the conducting zone which is not available for gas exchange due to thick membrane + some inspired air doesnt reach alveoli. In adult its ~150ml.

  • depends on size of pt - larger pt > greater ADS

• Alveolar dead space = present in patient with resp disease

  • It is vol of gas within respiratory zone where gas exchange does not occur (it would in normal patient so its 0ml)

• Physiological dead space = anatmical dead space + alveolar dead space.

  • Increase in physiological is mainly due to alveolar dead space as anatomical dead space is constant

• Increases significantly in certain lung diseases - primarily due to under perfusion of affected alveoli

  • e.g PE, pumonary hypotension due to blood loss.

• An increase in physiological dead space will decrease alveolar ventilation > impacts blood oxygenation, CO2 and pH

• Total (minute) ventilation is defined as volume of gas brethed in one minute. Calculated as:

  • Minute/total ventilation = Tidal volume x RR

• Due to anatomical dead space, not all of this ventilation reaches respiratory zone. AV is calculated as:

  • Alveolar ventilation = (Tidal Volume - Anatomic Dead space) x Respiratory Frequency

This is more useful way of measuring total ventilation in terms of gas exchange. This can be affected by changes in physiological dead space + breathing pattern.

Increases alveolar ventilation by decreasing the proportion of breath that is contained within the anatomical dead space

• COPD patients who may have increased alveolar dead space taught to breath via pursed lip breathing.

• Slow deep breathing increases tidal volume (vol of air breathed in/out in one min) = more air reaches alveoli, reducing dead space)

• Reduces RR > more time for gas exchange

• This can help improve movement of air in and out of the lungs, open airways and move trapped air, control RR, reduce anxiety and promote relaxation

Anterior body of T1 vertebra, medial borders of rib 1 (L+R) and superior border of manubrium

Trachea, oesophagus, major blood vessels and nerves

Descending oesophagus, descending aorta and ascending inferior vena cava

Anterior body of T12 vertebra, floating ribs 11/12, costal margin, Xiphoid process superiorly and anteriorly.

Sternal angle = angle of loui, its where the manubrium meets the body of sternum.

Horizontally it is at the level of T4,T5, it marks the area of beginning and end of arch of the aorta and bifurcation of bronchus to left and right

Ribs can be classified as typical and atypical (ribs 1, 11, 12)

They can also be classified as true, false and floating

• Ribs 1-7 - True ribs

  • Directly articulates with sternum via costal cartilage

• Ribs 8-10 - False ribs

  • Indirectly articulates with sternum via costal cartilage to rib 7. This forms costal margin

• Ribs 11-12 - Floating ribs

  • Do not articulate with sternum

1. Pump handle movement - increases volume of thorax, there is a superior and anterior movement of the ribs and sternum

2. Bucket handle movement - Elevates the rib and also increase thoracic volume. Occurs medially to laterally

Left lung

• has 2 lobes - superior and inferior lobe, separated by oblique fissure

Right lung

• Has 3 lobes - superior, middle and inferior lobe, seperated by horizontal fissure superiorly and oblique fissure inferiorly

Trachea is the conducting airway inferior to the larynx which ends inferiorly at lower border of cricoid cartilage (C6) an enters the thoracic cavity through thoracic inlet.

Carina is the bifurcation of the trachea at the level T4-T5.

Same as sternal angle.

(it is also the same level where arc of the aorta start and ends

Trachea bifurcates into right and left main bronchus

• R is steeper than left and slightly wider = high likely to get lodging of aspirated materials.

• The main bronchi then split into lobar bronchi

• 1st rib

• Left brachiocephalic vein

• Arc of aorta

• oesophagus

• descending aorta

Also has large indentation where heart would be

Hilum of the lung is the triangular depression located on the medial aspect of each lung. Structures (superior to inferior):

• Pulmonary artery

• Bronchus

• pulmonary vein

The pleura is a membrane around the lungs and the inside of the thoracic wall. It is a continuous layer but divided into:

• The parietal pleura, which lines the inside of the thoracic wall

• The visceral pleura, which lines the outside of the lungs.

It extends into fissures and continuous at the hilum.

Between the layers of parietal and visceral pleura, there is a small vol of serous fluid known as parietal fluid.

Function - prevents friction between the layers and lubricate them. Aslo helps to keep the layers against one another.

Rib # can be anterior or posterior

• Pneumothorax:

  • rib # can damage the surface of the lung > air entry into the pleural cavity. will affect the adhesive effect that couples the lung and thoracic wall > lung collapse

• Haemothorax:

  • if the # is severe, the sharp edges of the rib can damage the neurovascular bundle in the costal groove > blood building in the pleural cavity.

• Frail chest

  • this is where isolated section of the chest wall moves opposite direction to the chest wall - moves in during inspiration and out during expiration

• Tension pneumothorax

  • Air is drawn into the thorax but cant escape > increased pressure on the mediastinal structures

A pressure difference between alveolar pressure (PA) and barometric pressure (PB) (atmospheric).

• PB cant be changed so alveolar pressure is changed for pressure gradient

Boyle’s Law

• Pressure of a gas varies inversely with vol of the container of the gas - so if the vol is halved, pressure is doubled.

Alveolar pressure decreases below atmospheric pressure.

• This causes air to move into lung via inspiration.

Alveolar pressure increases above atmospheric pressure

• Decrease in lung vol > increase alveolar pressure > air moves out via expiration

Diaphragm

• Thoracic vol is altered primarily by movement of diaphragm.

• If larger changes in vol are needed, accessory muscles of inspiration and expiration is used.

External intercostals, scalenes, sternocleidomastoid muslces

• Contraction of these muscles causes changes in lateral, vertical and antero-posterior dimensions of thorax.

Internal intercostals and abdominal muscles

Visceral pleura - lines surface of the lungs

parietal pleura - lines inner surface of the thorax

> Work of breathing is done by respiratory muslces of thoracic cage and the pleural membrane couple these. Each lung has its own pleural membrane.

Pleural fluid (lubricating)

• Pleural space is the space between visceral and parietal pleira

• The vol of air in the lung at the end of normal expiration.

• Respiratory muscles are relaxed

  • lung coils inwards and pull away from thoracic cage

  • Thoracic cage recoild outwards away from the lung

  • This creates sub-atmospheric pressure in the intrapleural space which enables lung/thorax to adhere together

• At FRC, inward lung recoil = outward chest forc —> they are at equilibrium = no air flow.

• Clinical significance - COPD pt have high FRC due to hyperexpansion and air trapping. Restrictive lung conditions such as fibrosis has low FRC

Lung recoil Inwards and thoracic wall outwards

• Movement of the lung differes from the thoracic cage but it need to move with the movement of thoracic wall.

• Lung-thorax coupling is determined by the elastic properties

Opposing elastic recoil of lung and chest wall creates sub-atmospheric pressure

• the negative pressure causes the 2 pleural membrane (visceral and parietal) to push towards each other and adhere. —> so if chest wall moves outwards, lung will move with it

Inspiration:

1. Diaphragm flattens down —> increase throacic volume

2. This causes intrapleural space pressure to be more negative (-5 to -8) —> lung expansion

3. The increase in lung volume —> reduced alveolar pressure(PA) —> pressure gradient between the atmosphere (PB)

4. As per Boyle’s law, the air moves from the atmosphere into the lung down the pressure gradient

Expiration

1. Diaphragm relaxes —> reduces thoracic volume

2. Intrapleural pressure increases (-8 to -5) —> lung recoils

3. This leads to increase alveolar pressure (more compared to PB) —> pressure gradient moves air out of the lung

When alveolar pressure equals barometric pressure

• On the airflow trace, it is -ve during inspiration and +ve during expiration.

• during inspiraton, alveolar pressure is negative and its +ve during expiration.

• Intrapleural pressure is always negative but can be postive during forces expiration.

Note: at the 2nd red line, difference between PA and PB is the greatest (barometric remains constant but alveolar becomes negative) > lung wants to recoil and the intrapleural pressure is more negative. Airflow (V.) is 0 at 3rd red line as pt about to exhale = lung vol is at max = -ve IP and recoil pressure.

The change in volume per unit change in pressure - measure of how much a structure will change volume for a change in pressure.

• Measures lung’s ability to expand (‘distensibility):

  • high compliance = easy lung expansion (emphysema). Inc lung vol but reduced elastic recoil —> harder expiration (air trapping)

  • low compliance = stiff lung (fibrosis). Hard to expand lung > low vol and elastic recoil > rapid shalow breathing.

Pressure inside the lung minus pressure outside the lung which is intrapleural space (Pin - Pout).

Thoracic cage distending pressure is the pressure inside the intraplueral space minus the atmospheric / PB.

• If Pin is > than Pout = +ve distending pressure —> structures are distended (right of the graph)

• If P out is > than Pin= -ve distending pressure —> structures are compressied (Left of the graph)

• compliance of the lung and throacic cage are similar at FRC

• Equilibrium vol is where there is no distending or compression pressure

Around FRC

• This is where breathing is most easy.

Compliance divided by FRC

• Used when comparing different sizes e.g baby’s lung against an adult lung - both have similar compliance but different specific compliance

Lung compliance

• Graph lies to the right = lungs are always distended at any given volume. Normal lung compliance is ~1.5L kPa.

• It is lowest towards TLC - this causes issue in COPD / emphysema where pt have larger volumes > difficult to breath

Thoracic compliance

• Graph lies on the left = it is compressed (at high vol it becomes distended).

• Equilibrium vol is ~ 4-5L - chest wall have larger vol at DP of zero.

Total system compliance

• Lung lie within thoracic cage and both need to be stretched during inspiration so the TSC is considered.

** Any change in either lung or thoracic compliance will change FRC

• Increase in lung or wall compliance > increase FRC

• Decrease in lung or wall compliance > decrease FRC

It is lower (TSC is twice as stiffer than either component alone) - E.g if lung and thoracic compliance are 2, TSC would be 1 = half the compliance = twice stiff.

• At 0 distending pressure, TSC curve pass through Y axis - this is the value used as FRC. So at this point. DP of thoracic cage equals and opposite the DP of lung.

FRC increases

Any change in either lung compliance or thoracic cage compliance will change FRC:

• Increases in CW or CL will increase FRC.

• Decreases in CW or CL will decrease FRC.

Air in the pleural space causing loss of negative intrapleural pressure > causing lung and thoracic cage to move towards their equilibrium volume.

• It occurs if the lung perforates or there is penetrating wound of chest wall causing air from the lung or atmosphere to enter and fill the pleural space until thhere is no longer a negative intrapleural pressure.

• At this point the Ppl = PB = 0kPa

The lung collapses and the chest wall expands

• The Lung and Thoracic cage are not at the equilibrium volumes because they tend towards negative intrapleural pressure. Therefore if this pressure is lost, they will begin to move towards those equilibrium volumes

• Loss of distending pressure (Ppl = PB) means lung cant be expanded and thoracic wall cant be compressed.

• This leads to uncoupled breathing > painful, difficult or impossible at the site.

• Primary pneumothorax – Most common type of spontaneous pneumothorax , which occurs with no underlying condition and only requires outpatient treatment.

• Secondary Pneumothorax – A type of spontaneous pneumothorax which develops in someone with an underlying lung disease such as COPD or asthma. It tends to require intercostal tube drainage.

• most common type, occurs when large air pocket (bulla) forms on the surface of the lung and breaks > hole in visceral pleura > air leak into pleural space

• Bulla forms due to air leak within the alveoli > releases air into surrounding lung tissue

A pneumothorax with a one-way valve mechanism causing progressive air trapping (allows air to enter and not exit the plaural space)

• Occurs post blunt or penetrating chest trauma or due to mechanical ventilation

• Most severe form > air moves into pleural space > mediastinal shift > heart to compress and great veins compression shock due to low BP.

Rigidity and shape of the thoracic cage - changes in shape or rigidity will change chest wall compliance.

It changes chest wall shape > decreases compliance and increases the work of breathing.

• No disease is associated with increase in chest wall compliance.

Surface tension at the air-liquid interface

Lung compliance determined by several variables:

• Elastic properties of lung tissue (collagen, elastic fibres). Compliance curve flattens when these reach their elastic limit at higher vol (TLC)

• Surface tension forces which arises due to air-liquid interface. Later only exists in lung filled with air not fluid.

• If lung get filled with fluid instead of air > there will be no surface tension as there is no air-liquid interface > higher compliance.

Approximately two-thirds (60-75%)

There is no air-liquid interface, so no surface tension (its like a skin on the water where it meets air)

• surface tension is a collapsing force that must be overcome when lungs are inflated in air-filled lungs. More work needed to stretch the lung against surface tension.

Pressure = 2T / r (T= tension and R = radius)

• Surface tension - Alveoli are fluid lined spherical bubbles. The fluid creates tension (T) creating inward collapsing force. This force also generates an outwards pressure (P=2T/r) which counteracts the tension in the wall.

• The Pressure prevents the alveoli from collapsing - Tension is constant so as radius decreases (smaller alveoli), the internal pressure must increase to prevent collapsing.

Because pressure is inversely proportional to radius

• P=2T/r —> tension is constant so if radius is smaller, the internal pressure need to increase to prevent the alveoli from collapsing.

The mutual support of alveoli preventing collapse by shared walls

• Is the concept that alveoli co-exist as they are bounded by other alveoli, the tendency for one to collapse is prevented by the tendency of others to collapse.

• Shared connective tissue (collagen, elastin) - distributes stress > prevents collapse (atelectasis) and ensures uniform expansion.

Phospholipids (DPPC), cholesterol, and proteins

• It is a surface acting substance found in intestitial fluid, act as a detergent that lowers surface tension in alveoli.

• Surface tension of pure interstitial fluid is 70mN/m but surfactant drop it to <2mN/m

Type II alveolar epithelial cells that lines the alveoli

Dipalmitoyl phosphatidylcholine (DPPC)

It reduces surface tension and increases compliance

• Surfactant consists of glycerol backbone with phosphate and choline residues on one side and palmitate residues on other.

• Palmitate is hydrophobic (oily so stick out in water), phosphate and choline are hydrophilic —> Having both ends on the glycerol backbone lines the air-liquid interface.

• This prevents surface tension by preventing water molecule from getting to the air-liquid interface.

• Thus, it reduce alveolar surface tension > increased lung compliance > reduce work of breathing.

Note: paper clip will float on normal water surface but if surfactant (fairy liquid) added to the water then place the clip, it will sink due to lack of surface tension.

Surfactants can alter their surface tension lowering effect depending on the surface area.

In alveoli with smaller radii = lower surface area —> it causes greater reduction in surface tension.

DPPC is more dense in smaller radius > greater surface tension lowering effect.

Emphysema

• Lung compliance can increase (floppy)or decrease in disease, making it difficut to breath

Note: chest wall compliance can only decrease with disease, NOT increase.

Pulmonary fibrosis or congestion

• Lungs becomes stiff due to the tissue being harder to inflate.

Surfactant deficiency

• most common cause of reduced lung compliance

• Foetus has no air-liquid interface as O2 is delivered via placenta from the mother so surfactant is not needed.

• ~32-36 week gestation, surfactant lines the alveolar surface ready for air breathing post birth.

• RDS occurs in children who are born with lack of surfactant > low lung compliance = 10x stiffer > causes smaller alveoli to collapse as not stable.

• Causes: maternal DM, prematurity

Surfactant production occurs late in gestation (32-36 week) - so earlier the prematurity, worse outcome due to lack of surfactants

• Along with lack of surfactant, a fibrinous membrane may also form on the alveolar membrane, hindering diffusion across alveoli-capillary membrane.

• Infects expends lots of energy to inflate the lungs + lungs deflate quickly. This leads to:

  • hypoxia, hypercapnia, acidosis and exhaustion

Assessed by conducting an assay for phosphatidylcholines in amniotic fluid.

• Done in all elective induction + C-section to assess lung maturity pre procedure (delayed if low surfactant level).

Administration of glucocorticoids

• If infant develops RDS after birth, it is possible to instil surfactants into the trachea.

Damage to the alveolar-capillary interface reducing surfactant production

• Associated with pneumonia, sepsis, smoke inhalation > damage alveolar-capillary interface and alveolar type II cells > loss of ability to produce surfactants

• Sx similar to RDS in children (hypoxia, hypercapnia, acidosis)

The pressure difference required for a given airflow.

• lower resistance = lower pressure difference required for flow. Later is the difference between alveolar and barometric pressure.

• Increased resistance to breathing is the frequent cause of ventilatory impairment - e.g. Asthma

• The work of breathing has two components resistance and compliance

• Resistance has two components.

  • Most of the resistance to flow is by friction in the airways - airway resistance (80-90%). This is the air molecules rubbing against the wall > friction.

  • there is also resistance by lung tissue friction - viscous resistance (10-20%) this is the movement of the lung..

Normal airflow resistance is relatively low - ~0.2 kPa·L⁻¹·s

Resistance is inversely proportional to the fourth power of the radius.

Number 8, pi, L and viscocity are constant so the equation is simplified to that in red. —> doubling radius would decrease resistance by factor of 16.

The upper airways

• 1st graph - Trachea would have lower resistance than single bronchiole due to having larger diameter

• 2nd graph - however, total cross-sec area of the bronchioles is greater than the trachea = later respiratory generations have much lower resistance than earlier gen.

• Blockage in later gen will have less effect upper airway resistance compared to blocks in upper gen.

Increased airway resistance (e.g. asthma)

Intraluminal airway obstruction - occurs upon aspiration of foreign materials (esp children) or regurgitation of food/blood.

• Coughing can clear this obstruction - should be encouraged when chocking. If this is ineffective, bronchoscopic removal or Heimlich manoueuvre is needed.

• Later involves forcing diaphragm upwards in sudden sharp movement > sudden increase in airway pressure distal to the obstruction > clear it.

Other causes - Bronchospasm (asthma), mucus secretion, oedema, tongue falling back when LOC can all lead to upper airway obstruction (managed by recovery position).

• Only accounts for 20% of airway resistance.

• Prime target in COPD - which is progressive and can be severe at the time of diagnosis. This is because the lower airways have little resistance so pt remain in ‘silent zone’.

Increased vagal parasympathetic activity

• Smooth muscles in the airway are under control of ANS - brochial diameter is under involuntary control.

Bronchoconstriction can be caused by:

• Increased vagal parasympathetic activity (30% tone at rest). This also induces mucus secretion.

• Local chemical mediators such as histamines and leukotrienes. These may be released in response to inflammatory or infectious diseases

• Decreased airway CO2. This may occur due to hyperventilating

Activation of β2-adrenoceptors by adrenaline or sympathomimetics.

Non-adrenergic, non-cholinergic (NANC) innervation.

• Due to the inverse relationship between airway diameter and airway resistance.

• As the diameter of an airway decreases, the resistance to airflow increases.

• However, the number of smaller airways in parallel reduces the total resistance to airflow, making the overall resistance less than that of larger airways.

• This is because the resistance in an airway is inversely proportional to the radius of the airway. Therefore, despite the smaller diameter of the terminal bronchioles, the high number of bronchioles compared to the larger airways means that the bronchi have greater resistance because there are less of them compared to the terminal bronchioles.

• airway contains smooth muscle which allows the radius or diameter of the airway to be controlled physiologically.

• Contraction of the smooth muscles causes bronchoconstriction and relaxation causes bronchodilation.

The physiological controls as follows:

1. Parasympathetic innervation (ACh on M3 receptors) —> Bronchoconstriction

2. No direct sympathetic but via adrenaline > B2 recep —> bronchodilation

3. NANC innervation (VIP/NO) or Sustance P —> Bronchodilation or bronchoconstriction

4. Mast cells —> bronchoconstriction

5. Mechanical receptors RAR or PSR —> constriction or dilation

6. CO2 —> bronchodilation

Airway smooth muscles are under ANS control

Parasympathetic innervation:

• efferent pre-ganglionic fibres run in vagus nerve > ganglia found in walls of the airways.

• Post ganglionic fibres release Ach which acts on muscarinic M3 receptors on the resp SM > contraction / bronchoconstriction

Sympathetic innervation:

• SNS do not innervate the SM of the airway but alter the diameter by releasing adrenaline from the adenal medulla.

• Adrenaline > blood > acts on Beta2 receptors > relaxation of SM > bronchodilation. Also inhibits mast cell activity (usually causes bronchoconstriction in response to allergen).

• In the ciliated epithelium, adrenaline increases activity of muco-ciliary escalator by increasing ciliary beating frequency (CBF) > helps remove objects from airway.

• Atropine - muscarinic antagonist > inhibits bronchoconstriction > reduce airway resistance by 30%

• Cigarette (nicotine) - causes bronchoconstriction and increased airway resistance.

• Part of ANS- innervates SM of trachea.

• Involves release of neurotransmitter that are not adrenaline or ACh - they have constrictor or dilator effect.

• VIP (vasoactive intestinal peptide) and NO > SM relaxation > bronchodilation

• Substance P > SM contraction (asthma) > bronchoconstriction.

Mast cells are stimulated by allergen > degranulation > release their secretory products (spasmogesn) onto SM > direct bronchoconstriction.

• Secretory products are - Histamine, platelet activating factor and leukotrienes

Mast cells also release chemotaxins > stimulate surrounding eosinophils and neutrophils to release spasmogens:

• leukotriens, plt activating factor and eosinophil major basic proteins

• These lead to bronchoconstriction - involved in astham attack.

Both act via vagovagal reflex (afferent and efferent arms of vagus nerve)

• RARs (rapidly adapting receptors)/cough receptors – Stimulated by foreign bodies or chemical irritants in the airway, stimulate bronchoconstriction

• PSRs (slowly adapting pulmonary stretch receptors) – Stimulated by stretch (e.g. during deep inhalation), and cause bronchodilation

CO2 builds up in poorly ventilated areas of the airway.

When this happens, the CO2 stimulates bronchodilation, thus improving ventilation

• Lung vol is powerful determinants of airway resistance - As Vol increase, total cross-sec area of the airway increase via radial traction / interdependence > reduce resistance.

• As Vol increases from RV to TLC - resistance decreases

• The effect is more marked during deep inhalation and exhalation compared to regular breathing as they lead to greater vol change. 2 reasons for this effect:

  • 1. Radial traction - Bronchioles are surrounded by dense interconnected network of lung parenchyma (alveoli) > keeping it open all the time (FRC). During inhalation, alveoli inflate > pull on large airway > dilate

  

  • 2. Alveolar interdependence - Alveoli shares their wall with neighbouring alveoli —> tendency for one to collapse is countered by another’s, keeping them open. During inhalation, each alveoli inflates, pulling open the smaller and nearby airways / alveoli

The effects of radial traction and alveolar interdependence are lost in COPD - where alveolar walls are damaged > increased resistance.

-> Asthma > SOB due to increased airway resistance due to bronchoconstriction.

-> Asthmatics have bronchial hypersensitivity due to inflammation of the mucosa which thickens due to infiltration of inflammatory cells which release spasmogens > constriction during an attack.

-> During an attack, there is also increased level of airway secretions > increased airway resistance by narrowing lumen.

-> Beta2-agonist e.g Salbutamol, salmeterol / terbutaline

• stimulates the B2 receptors on the SM of the airway > stimulates Gs pathway > activates adenylyl cyclase > cAMP > PKA > phosphorylation of MLCK > prevents SM contraction > SM relaxation = bronchodilation.

-> B2-agonists also act on inflammatory cells, preventing release of spasmogens and reducing inflammation.

2 types of B2-agonist used in asthma Rx (airway resistance)

-> Salbutamol

• Short-acting > bronchodilation.

• Side effects - tachycardia, tremors, airway hypersensitivity

-> Salmeterol/terbutaline

• slower onset, long-acting - not for acute attack.

• Terbutaline is safest in pregnancy

-> Inhibit phosphodiesterase (PDE) > increase cAMP > activates PKA > inhibits MLCK > promotes SM relaxation > bronchodilation (impacts airway resistance).

-> also have anti-inlammatory effect

-> Drugs - Theophyline and aminophylline

• given orally, high efficacy but have very narrow therapeutic window

• Side effects - headache, restlessness, arrhythmia, GI Sx

• Declining use due to multiple drug interaction

Anti-cholinergic / muscarinic antagonists (impacts airway resistance)

-> muscarinic recep are widespread in the body so selectivity is difficult - inhalation therefore has specific antagonistic effect on the muscarinic receptors on the airway SM.

-> Ipratropium

• Used to Rx asthma, blocks ACh effect on M3 receptors on SM > prevents SM contraction > bronchodilation.

• Ipratropium has quaternary nitrogen in its structure which prevents systemic absorption > reduced side effect.

• Side effects - dry mouth, altered taste and cough

1. Coricosteroids - e.g. beclomethasone

2. Leukoteriene pathway drugs - e.g montelukast

3. Sodium cromoglicate / cromolyn

4. Histamine receptor antagonists- e.g Ketotifen

5. Monoclonal anti-IgE Ab - e.g Omalizumab

-> Reduce inflammation and hyper-responsiveness by supressing gene involved in inflammatory response.

-> this reduces frequency and severity of attacks = preventative

-> E.g Beclometasone - an inhaled cortiocsteroids, activcated within the tissue lumen - this reduces systemic side effect.

• Mast cells produce spasmogens such as leukotrienes > inflammation + bronchoconstriction. Drugs can inhibit this pathway either by:

• 1. Inhibit formation of leukotrienes - e.g zileuton —> given PO, inhibits 5-lipoxygenase enzyme. Has short half-life

  • Can be used primarily in aspirin induce asthma where there is upregulation of 5-lipoxygenase > high leukoteriene elvels > rhinorrhoea, nasal congestion, sinusitis.

• 2. Inhibit leukotriene receptors - e.g. montelulast —> given PO as a single dose, Rx severe, exercise induced asthma

• When inhaled, Inhibits release of inflammatory mediators

• Also inhibits RAR reflexes (bronchoconstriction due to irritant / foreign body)

• Reaches maximal effect after 4 weeks of Rx

• Mild side effects - cough, wheeze, dry throat

• Taken PO e.g. Ketotifen

• Antagonise H1-receptors > anti-inflammatory effects.

• Maximal effect after 6-12 weeks Rx

• SE - drowsiness

• IgE Ab are released by B-cells in response to allergen > stimulates mast cells to release spasmogens and chemotaxins

• Anti-IgE Ab > reduce circulating level of IgE Ab > anti-inflammatory and bronchodilator effect

• E.g. Omalizumab - given SC every 2-4weeks. Only used in severe allergic asthma due to anaphlaxis as SE.

• Reliever drugs (e.g. Beta-2 agonists) reduce airway resistance by causing bronchodilation and are used acutely to treat the symptoms of an asthma attack.

• Reliever drugs (e.g. corticosteroids, leukotriene antagonists, histamine receptor antagonists, monoclonal anti IgE antibodies) work to reduce inflammation and hypersensitivity of the airways thereby increasing effective airway diameter but also reducing the chances of an acute asthma attack or exacerbation of asthma.

The connective tissue between lung epithelium and capillary endothelium (lining of blood vessel).

• Consits of alveolar epithelium, capillary endothelium, basement membrane, perivascular tissue and laymphatic tissue which surrounds the alveolar space

• O2 and CO2 must diffuse across the interstitium (parenchyma) to exchange between alveoli and blood.

• Usually it is thin > high rate of diffusion.

• But can be thick in disease > impairs exchange

  • For an adequte gas exchange, we need good alveolar ventilation, pulmonary circulation and functioning alveoli.

• Bronchovascular (axial) - Surrounds bronchi, arteries, veins until the bronchioles.

• parenchymal (acinar) - Between alveoli lining and capillary basement membrane

• subpleural interstitium - between pleura and lungs, and interlobular septa

It increases diffusion distance for oxygen and carbon dioxide.

• A disease which affects the interstitium is known as interstitial lung disease, this typically results in scarring.

• Interstitial/parenchymal scarring is known as pulmonary fibrosis

Scarring of the lung interstitium/ parenchyma

Aetiology:

• widespread - drugs / carcinomatosis

• Upper - TB, ankylosing spondylitis, sarcoidosis, hypersensitity

• lower zone - idopathic, connective tissue disease, occupational (asbestosis)

Restrictive lung disease

• Means, it reduces effective lung volume and surface area for gas exchange.

It remains normal or increased

The typcial spirometry results as follows:

(Restrictive patter with reduced TLC and reduced DLCO)

• Reduced FVC (<80% of normal)

• Reduced FEV1 (<80% of normal)

• Normal FEV1:FVC ratio (>0.7)

• Reduced TLC (total lung capacity)

• Reduced RV (residual volume)

• Reduced DLCO (gas transfer)

Split into 2 main categories:

-> Intrapulmonary disorders (affects lung tissue)

• Pulmonary fibrosis, inflammation/infection, sarcoidosis (Granunomas - lumps of inflammatory cells in the interstitium), and atelectasis (collapse of part of lung)

• Spirometry - decreased FVC, FEV1, TLC and RV, normal or elevated FEV1:FVC ratio. Decreased diffusion (DLCO)

-> Extrapulmonary disorders

• Pleural cavity disorders, Neuromuscular disorders

• Chest wall deformities, Obesity

• Spirometry - same as above except Normal diffusion (DLCO)

• Inflammation/infection

• Sarcoidosis - Granulomas (lumps of inflammatory cells) in the interstitium

• Atelectasis - Collapse of part of the lung

• Pleural cavity disorders – such as pleural thickening due to asbestos exposure, calcified pleural plaques, pneumothorax, or pleural effusion.

• Neuromuscular disorders – involving innervation to respiratory muscles, i.e. ALS

• Chest wall deformities – such as pectus excavatum or kyphosis.

• Obesity – leading to splinting of the diaphragm, or ascites.

Idiopathic pulmonary fibrosis (unknown cause)

• Fibrosis is an outcome of ILD - scarring of lung parencyma usually post inflammation.

• Pulmonary fibrosis is an umbrella term for >200 diseases with different pathogeneses > loss of function and resp failure.

• Aetiology of fibrosis can be UL, LL or widespread

• Idopathic is most common in middle-aged pt, > in men

Approximately 3 years

• PF affects 50/10k a yr - 16% are idopathic, 40% autoimmune (RA, connective tissue disease, systemic lupus, sclerosis and sarcoidosis)

• RA is a big risk factor

• High mortality with survival rate worse than lung Ca

• Sx - Dyspnoea on exertion and chronic dry cough

• SH - smoking, asbestose, silica

• PHM - ?connective tissue disease, sarcoidosis, TB, drugs (amiodarone or nitro), RT for Ca, recurrent aspirations

• Exam - inspiratory crackles at the bases (do not change after coughing), rheumatoid hads, finger clubbing

• Spirometry - Low FEV1, FVC, gas transfer, alveolar vol, RV and TLC. Normal FEV1/FVC ratio.

History specific to upper lobe fibrosis (S-CHAARTS)

• Silicosis/Sarcoidosis

• Coal worker’s pneumoconiosis

• Histiocytosis

• Ankylosing spondylitis

• Allergic bronchopulmonary aspergillosis

• Radiation

• Tuberculosis

• Smoking

History specific to lower lobe fibrosis

• Rheumatoid arthritis

• Asbestosis

• Scleroderma

• Idiopathic pulmonary fibrosis

• Drugs: busulphan, bleomycin, nitrofurantoin, hydralazine, methotrexate, amiodarone

Reticular nodular shadowing - seen in suspected ILD

Subpleural reticular shadows - ILD

Image 1 - Traction Bronchiectasis

• Complication of late pulmonary fibrosis where the airways are pulled pary and dilated

Image 2 - Honeycombing

• Feature of advanced pulmonary fibrosis

Early-stage fibrosis

• Scarring or laying down of collagen in the parenchyma is not yet established

• On-going inflammation in the lung tissues, can be associated with ground glass change on CT.

• This type responds to Rx and may improve

Localised fibrosis vs ground glass

Distribution of scarring is key to Dx the type of fibrosis

• Idopathic - lung bases are affected more, there is a prominent apical-basal gradient

• Hypersensitive pneumonitis - due to allergens, upper zones

• Sarcoidosis - upper and middle zones with lymphatic nodules

• Rheumatoid profile - RhF / anti-CCP test ?RA

• Autoimmune - ANAs, ANCA and ENAs ?systemic lupus or CT diseases (pt often develops lung Sx 1st)

• Hypersensitivity - Fungal precipitants, asbestose, silica

If cause is still not clear, further Ix:

• Bronchoalveolar lavage – instillation > extraction of fluid into LRT for analysis (cell count, lymphocyte/eosinophil)

• Transbronchial biopsy – telescope inserted into trachea, needle used to extract tissue biopsy.

• EBUS-guided lymph node biopsy – US-guided lymph biopsy.

• VATS (video assisted thoracic surgery) lung biopsy – camera and surgical tools inserted through incisions in the chest wall to extract a tissue biopsy.

Usual interstitial pneumonia (UIP)

• Could be due to end-stage fibrosis of other aetiologies (CT disease, RA or toxins)

• Associated with basal / peripheral / sub-pleural pathology, ground glass change as fibrosis establishes > honeycombing. Ab or blood test NAD

Honeycombing

Airway dilation due to fibrotic pulling of bronchial walls

Rheumatoid factor, anti-CCP, ANA, ANCA, ENA

Basal and subpleural fibrosis with honeycombing and minimal ground glass change

• Idiopathic pulm fibrosis is chronic, progressive, fibrosing interstitial pneumonia of unknown cause. Most commonly it leads to UIP histological pattern associated with honeycombing and reticulations on CT

NSIP has a better prognosis

• NSIP is a different type of radiological finding of idiopathic pulmonary fibrosis or other aetiologies (CT/toxin). Includes:

  • Absence of other aetiology findings on radiology

  • Reticulations, ground glass change, unvarying districbutiion

Currently 2 drugs are licensed:

1. Pirfenidone (5-methyl-1-phenylpyridin-2-one) - inhibits TGF-beta stimulated collagen synthesis > reduce ECM deposition. Aslo inhibits fibroblast proliferation > reduce deposition of collagen leading to fibrosis

2. Nintedanib - Inhibits intracellular tyrosine kinase which is key for inflammatory process + upregulation of GF.

NICE recomends these drug use for pt with IPF if they have FVC 50-80% of expected - Rx must be stopped if disease progress to FVC decline of 10% or more in 12 months.

Inhibition of intracellular tyrosine kinase pathways

• Pulmonary rehabilitation - In addition to drug, involves maintaining fitness, muscle bulk, and nutrition.

• Oxygen therapy – in patients with low oxygen levels.

• Support groups – to understand disease and feel empowered and supported.

• Smoking cessation – in patients who smoke.

• Palliative care and end of life planning – in a progressed form of disease

This type of ILD is caused by inhalation of organic particles, which could be for example:

• Hay fungi (Farmer’s Lung)

• Bird proteins (Bird Fancier’s Lung)

• Various fungi (Mushroom Worker’s Lung)

This leads to antibody formation (precipitins) and T-cell sensitization.

This leads to type III or type IV hypersensitivity reaction within lung tissue, causing damage.

Type III or Type IV hypersensitivity

Acute presentation

• Post exposure to organic particles > acute Sx of dry cough, hypoxia, fever, myalgia within 4-8hrs.

• Responsive to steroid Rx within 48hrs with full recovery.

• Presentation occurs after short, intense exposure

Chronic presentation

• Progressive SOB with irreversible lung damage including fibrosis. (similar to IPF) due to long term / low-grade exposure to risk factor

• Rx involves anti-fibrotic drugs - Pirfenidone / nintedanib

Subacute presentation

• Between acute / chronic

Antigen avoidance - often sufficient to Rx the disease

Other Rx - steroids in acute or subacute presentation

Anti-fibrotic drugs in chronic phase

Respiratory bronchiolitis and desquamative interstitial pneumonitis (DIP) are associated with smoking and emphysema.

Rx involves smoking cessation.

Cryptogenic organising pneumonia (COP)

• Associated with more acute onset and with RA

• Responds to steroid Rx

GLD is a class of lung disease associated with formation of granulomas (lumps of immune cells) in response to infection or inflammatipn. Could potentially lead to ILD / fibrosis

Different causes are:

• Infection – such as TB or fungi

• Inflammation – such as sarcoidosis and extrinsic allergic alveolitis/hypersensitivity pneumonitis (EAA/HP)

• Vascular disease – such as Churg-Strauss, Wegener’s granulomatosis, or polyarteritis nodosa.

Non-caseating granulomas

• Sarcoidosis is a multi-system, non-infectious inflammatory disease of unkown aetiology

• Associated with non-caseating granulomas (no necrosis)

• Common in afro-caribean (3x)

• Rx (rule of 3rds) - 1/3 better without steroids, 1/3 better with short course steroids, 1/3 need LT steroids

A chest x-ray may show:

• Hilar lymphadenopathy (enlargement of lymph nodes around lung hilum).

• Infiltrates of granuloma into the lung tissue itself

• Fibrosis of lung tissue

This helps to stage the disease:

• Stage 0 – Normal Chest X-Ray

• Stage 1 – Granulomas in lymph nodes only

• Stage 2 - Granulomas in lymph nodes AND lungs

• Stage 3 – Granulomas in lungs only

• Stage 4 – Pulmonary fibrosis or scarring

-> This is a complication of sarcoidosis with traid:

1. Bilateral hilar lymphadenopathy

2. erythema nodosum - tender, red bumps on shins

3. polyarthralgia - pain in 2 or more joints

In 85% cases these Rx resolve spontanously and may arise 2 yrs prior to lung manifestation of sarcoidosis

• Skin – Tender red/brown/purple bumps.

• Eyes – Inflammation, yellow bumps on eyes, seeing black spots or strings, sensitivity to light, red and painful eyes, blurred vision.

• Heart – arrythmias, tachycardia, heart block, cardiomyopathy, heart failure.

• Neurological – Headaches, ataxia (poor muscle co-ordination), fatigue, nausea, vomiting.

• Liver – Abdominal pain, itchy skin, weight loss, fever, hepatomegaly (enlargement of liver), jaundice.

In addition to CXR, other Ix includes - spirometry, HRCT, ECG

Rx - steroids, steroid-sparing immunosuppressant drugs (to reduce LT complications), new anti-inflammatory monoclonal Ab e.g. infliximab

• This is an inflammation of the blood vessel > obstruction or bleeding. May affect pulmonary capillaries in the interstitium > diffusion abnormalities and inflammation of the lungs.

• More common due to renal diseease or due to multisystem disease

Types of vasculitis affecting lung:

• Wegener’s granulomatosis – inflammation of blood vessels leading to granulomas.

• Goodpasture’s disease – vasculitis affecting glomerular and/or pulmonary capillaries.

Pulmonary haemorrage = Bleeding within the lung tissue. This is a possible cause of interstitial lung disease.

It is associated with:

• Dyspnoea (difficulty breathing)

• Haemoptysis (coughing blood)

• Opacity in chest X-ray

• High gas transfer as result of pulmonary function tests, due to leakage of blood

The extent of a pulmonary haemorrhage can be visualised by bronchoscopy.

Haemoptysis

ANCA (anti-neutrophil cytoplasmic Ab)

• Also known as Wegener’s granulometosis.

• Associated with inflammation of blood vessels > granulomas and multi-organ damage.

• Complications affecting UL - granulomas causing bleeding, sinusitis, saddle nose due to septal destruction by granulomas.

• Complications of the lung - haemorrhage and cavities.

• Dx - ANCA +ve

• Rx - high dose immunosuppression.

-> PiO2 = 20 kPa (approximately 19.7 kPa when corrected for water vapour)

-> PiCO2 = 0kPa

-> In the conducting zone, partial pressure of O2 and CO2 are different during inspiration and expiration.

• Inspiration - PO2 is 20kPa, PCO2 is 0

• Expiration - PO2 is 13kPa and PCO2 is 5kPa

  • Pressure of O2 reduced and CO2 increased

PAO₂ ≈ 13 kPa, PACO₂ ≈ 5 kPa

• Alveolar space is different to conducting zone in that the pressure of O2 and CO2 remains constant during inspiration and expiration

Because the alveolar volume is large and fresh air mixes mainly by diffusion

• This is due to large vol of alveolar space (total Vol 2.5L)

• Each breath brings only about 350ml of fresh air - relatively small vol compared to alveolar vol

• The fresh air mixes with alveolar air only via diffusion (unlike in conducting zone where there is a massive flow)

• The gas tension in the alvoli remains stable

PvO₂ ≈ 5 kPa, PvCO₂ ≈ 6 kPa (varies depending on metabolic rate)

• Blood arriving to alveoli via pulmonary artery (classed as venous blood) has lower O2 and higher CO2 pressure than alveoli

• This allows gas exchange between alveoli and blood down the pressure gradient > stablise to aveolar gas pressure

• This sents the PCO2 and PO2 leaving the lung

PaO₂ ≈ 13 kPa, PaCO₂ ≈ 5 kPa (small a = arterial, A = alveolar)

• After gas exchange, the blood from the pulmonary artery stablises to aveolar pressure and the arterial blood leaving the alveoli have higher O2 pressure

While alveolar gas pressures are stable between inspiration and expiration, they can be varied by changes in:

• Alveolar ventilation – Increasing alveolar ventilation decreases PA CO2, and vice versa. Therefore, PA CO2 is inversely proportional to alveolar ventilation, V̇A.

  • If ventilation is increased, it dilutes the PACO2 and high RR > blow out CO2 faster > low PACO2

• Metabolic rate (V.CO2) – Increasing V.CO2 increases PA CO2, they are therefore proportional.

  • If more CO2 comes into the lung due to increased metabolism > it diffuse into the alveoli > increased PACO2

equation above is derived by simplifying:

1. alveolar CO2 (PACO2) is proportional to metabolic rate (V.CO2) = if one goes up, the other goes up - vice versa

2. Alveolar CO2 (PACO2) is disproportional to alveolar ventilation (V.A) = if ventilation goes up, PACO2 goes down and vice versa.

It decreases PACO₂

• Increasing ventilation beyond the body’s requirements (hyperventilation) will decrease PACO2, decreasing ventilation (hypoventilation) > drastically increase PA CO2

Note: By keeping PACO2 (alveolar) constant at 5kPa, the PaCO2 (arterial) remains at 5kPa. So measuring PaCO2, adequacy of alveolar ventilation (V̇A) can be clinically evaluated.

I.e. If PaCO2 is too high = alveolar ventilation is insufficient to match bodies demand

It increases PACO₂

• Physical activity > increased VCO2

On the graph - if we increase the metabolic rate and not increase the ventilation, the hyperbola shifted upwards = VCO2 has doubled (bule arrow).

• In reality, when we exercise, the breathing / ventilation increases in direct proportion to the metabolic rate > the alveolar CO2 remains constant (red arrow)

• It is therefore important to match the ventilation to the metabolic rate

I.e. If PaCO2 is too high = alveolar ventilation is insufficient to match bodies demand

• Increasing alveolar ventilation (V̇A) increases PA O2.

• Increasing metabolic rate (VO2) decreases PA O2.

This relationship is opposite to the PACO2 and can be applied using the equation: (note its minus PiO2 which is ~20kPa)

It increases PAO₂

PAO₂ = PiO₂ − (PaCO₂ / RQ)

• Derived from combining equation of PACO2 and PAO2 and substituiting using the formula for RQ

• PiO2 is estimated at 37C = PiO2 = (PB – PH2O) x FiO2 = 19.68 kPa at sea level.

  • Where PB is barometric pressure, PH2O is water vapour pressure, and FiO2 is fractional concentration of oxygen in the air (0.21).

• R (or RQ) is assumed to be 0.8 in a normal diet.

• PA CO2 is assumed to be equal to Pa CO2 (arterial), which can be measured from a ABG

  • e.g. PAO2 = 19.68 - (ABG CO2 - 0.8)

So if the PACO2 goes up, the PAO2 goes down then by increasing the PiO2 will help to bring the levels back to normal.

Approximately 1 kPa

• Value of calculated PAO2 will always be 1kPa higher than actual PaO2 measured from ABG

• Magnitute of the alveolar-arterial PO2 difference is the PA-aO2 difference. So if the difference is more than 1kPa = impaired respiratory system.

Hypoventilation

Alveolar epithelium, basement membrane, capillary endothelium

The square root of molecular weight

CO₂

About 20 times faster

A gas that does not equilibrate with alveolar pressure during capillary transit time

Carbon monoxide (CO)

A gas that equilibrates rapidly with alveolar pressure and whose uptake depends on blood flow

Nitrous oxide (N₂O)

About 0.75 seconds

Increased cardiac output reduces transit time but oxygen still equilibrates due to diffusion reserve

Oxygen may fail to equilibrate, causing hypoxia even at rest

DL = V̇ / (P₁ − P₂)

Because its capillary partial pressure is effectively zero due to high haemoglobin affinity

Approximately 175 ml·min⁻¹·kPa⁻¹

Pulmonary fibrosis and pulmonary oedema

Exercise and pulmonary haemorrhage

Because oxygen diffusion is more easily impaired despite CO₂ being more soluble

Second rib - articulates anteriorly

• Aka angle of Louis = inferior to the sternal notch where menubrium meets sternum. Anatomical relevance here:

  • Bifurcation of trachea, aortic arch begins & ends and azygous vein enters SVC

Tracheal bifurcation, beginning and end of the aortic arch, and entry of the azygos vein into the superior vena cava

Three (upper, middle, lower) - divided by horizontal fissue superiorly and oblique fissue inferiorly.

• These further seperates into 10 segments

Two (upper and lower) - divided by oblique fissure

Approximately 72%

• Other risk factors - HIV, prev RT, pulmonary fibrosis, asbestos and familial.

• Poor cure rate (<7%) due to late presentation / Dx

• Currently no NHS screening programme

Persistent cough and haemoptysis (others include weight loss, dyspnoea, chest pain, hoarse voice due to cancer infiltrating into recurrent laryngeal nerve)

• Clinical signs - finger clubbing, cervical / suraclavicular LN, SVC obstruction > facial swelling

Chest X-ray - ? pulomary nodule ?pleural effusion / lung collapse

CT scan

-> ?mets to other organs

-> ?secondary nodule / LN involvement

To detect metabolically active (malignant) tissue and metastases - will appear brighter / red

-> Look for nodules that are not clear on CT, to R/O benign nodule (wont appear bright)

Bronchoscopy (inserted through trachea)

• ? type of cancer base on histology

• US probe can be used to guide biopsy (EBUS)

Pic: Left is normal, middle & right has tumour

TNM classification (Tumour, Node, Metastasis)

• Determines treatment options and mortality.

• Stage 4 once metastasis.

Non-small cell lung cancer

-> Adenocarcinoma (38%)

-> Squamous (20%) - originates from squamous cells of bronchi, locate centrally, common in smokers. Can cause high Ca2+ by stimulating PTH release

-> Large cell (5%) - central / peripheral

-> Other

Small cell lung cancer

->Poorly differentiated cells, located centrally, metastasise easily

-> Originates from small, immature neuroendocrine cells

-> Common in heavy, LT smokers

-> Can lead to Cushings-like Sx due to ectopic ACTH secretion / SIADH due to ADH secretion.

SC lung ca may lead to Lambert-Eaton syndrome, caused by autoimmune damage of NMJs, leading to myasthenic symptoms (e.g. muscle weakness, eyelid drop and fatigue).

Adenocarcinoma (a type of non-small cell lung cancer)

• tumour of mucous-secreting cells of bronchioles. More peripheral, metastise early, responds to chemo. Common in young, non smokers

Small cell lung cancer

Lobectomy (also wedge resection or pneumonectomy)

• Surgery offered if pt is fit and tumour is resectable (stage I-IIIa) and is confined to an area.

• Surgery offeres best prognosis. Options:

  • Lobectomy - entire lobe of affected lung removed

  • Wedge resection - area within a lobe is resected

  • Pneumonectomy - removal of entire affected lung

In patients unfit for surgery or as adjunct therapy in stages I–III.

• Can be used in combination with chemo - Chemo+surgery , Chemo+RT or palliative chemo for late stage ca

Limited and extensive

• Limited - cancer is confined to only one lung (ipsilateral hemithorax) and supraclavicular lymph nodes

• Extensive - if it spreads elsewhere

Treatment:

• Surgery for limited cancers, chemo and RT

• Drain pleural effusion if symptomatic, opiates for cough, analgesia, dex of brain mets

Brain and bones (also pleura)

• Metastase via blood or lymphatics

Raised JVP and facial swelling (also cyanosis, collateral veins e.g azygos-hemiazygos)

Miosis (constricted pupil) and ptosis (droopy eyelid), anhidrosis (lack of sweating), enophthalmos (sunken eyes), hoarseness of voice due to danage to recurrent laryngeal nerves

• Due to unilateral damage to sympthatheic innervation of the head

Dull percussion note and reduced vocal resonance, reduced expansion, pain, SOB

• Occure due to fluid build up within pleural cavity - due to leakage of fluid into pleural space / reduce clearance.

Transudate has low protein content; exudate has high protein content

Asbestos exposure e.g. plumbing, building, insulation)

• Mesothelioma is a cancer of pleura lining the lungs

• Sx - pain, pleural effusion

Pleurectomy (also pleurodesis or extrapleural pneumonectomy)

• other Rx - chemo, RT, immunotherapy

Approximately 13 kPa

Approximately 12 kPa

About 1 kPa

• It is the natural diffferences in PO2 of alveoli vs artery

• This gradient doesnt apply for CO2 due to high diffusibility

• Blood arriving the lung via pulmonary artery has low PO2 of ~5Kpa, as it leaves the lung, it equilibrates with alveolar PO2 to 13kPa > heart.

• The oxygenated blood that get pumped out the heart via aorta has PaO2 of 12kPa

Physiological shunts

-> Refers to blood returning to LA before it can be oxygenated by lungs mixes with oxygenated blood > reduces total PaO2

V/Q mismatch

-> At rest, pulmonary ventilation (V.) is ~4L/min. Cardiac output to the lung provides blood flow (Q) of ~5L.

-> This lead to natural 0.8 V/Q ratio at rest = lungs not able to oxygenate all the blood due to limited ventilation.

A-a gradient increases naturally with age due to increase V/Q mismatch.

-> To predict someone’s A-a gradient, divide age by 30 +0.3

-> Refers to deoxygenated blood mixing with oxygenated blood in the LV before being pumped out to systemic circulation.

-> This lead to reduce PaO2 > A-a gradient.

Natural R-L anatomical shunts (only affect <2% of cardiac output) are:

• Thebesian veins = small veins that drains deoxygenated blood from heart wall > chamber > mix with oxygenated blood in LV

• Bronchial circulation = Thoracic aorta branches supplies oxygenated blood to bronchi, tissues use it > deoxygenated as there is no gas exvhange in bronchi.

  • This blood from bronchopulmonary vein drains > pulmonary vein > LA > mixing with oxygenated blood in LV.

-> Refers to blood that reaching alveoli via pulmonary capillaries does not get oxygenated due to a pathology.

-> Higher degree of shunt > higher A-a gradient > low PaO2

Occurs in pulmonary disease:

• Airway block = e.g. foreign body or mucus > reduced / no ventilation downstream > alveoli unable to transfer O2

• Collapsed bronchioles or alveoli = impairs gaseous exvhange in affected pulmonary capillaries

-> Anatomical abnormalities > oxygenated blood from left heart mixes with deoxygenated blood from R heart.

-> An opening > blood from higher-pressure systemic circulation (LA, LV, aorta) leaking into lower pressure pulmonary circulation (RA, RV, pulmonary artery).

-> Increase blood flow in pulmonary circulation > congestion & pHTN. L-R shunts can occur due to:

• Atrial or ventricular septal defect - incomplete closure of atrial or ventricular septa > mixing blood / flow from L>R

• Patent ductus arteriosus - Developing fetus receives blood from placenta so the lungs not being used for gas exchange. So some blood drain into aorta via connection - the ductus arteriosus.

  • This normally closes after birth - but in some it doesnt > blood from aorta drain into pulmonary artery instead of reaching systemic circulation

It increases from base to apex

• Throughout the lung tissue, V/Q varies as both ventilation and perfusion vary.

  • Variation in ventilation is caused by gravity & compliance = apex get pulled (retracted) down from the chest wall than base vs bases pushed towards.

  • Retraction > more -ve intrapleural pressure in apex > inc lung vol at FRC = alveoli in apex are more inflated > less compliance in apex

• So when breathing in, distending pressure > greater vol change for base than apex = greater air flow (V.) = greater ventilation to bases.

• Base of the lung receives 2.5x more ventilation than apex and 6x more perfusion than apex. = ventilation and perfusion decrease moving upwards from base > apex

• At the lower lung, Q>V —> V/Q <1

• Moving upwards, the perfusion falls at higher rate than ventilation. So V/Q is lowest at the base (V/Q = 0/6)

• At some point in the lung between base and apex, V=Q so V/Q = 1. Beyond this point,V>Q so V/Q ratio is >1 near the apex (V/Q=3)

• Summary - V/Q increases mvoing upwards from base to apex. Most of the lung tissue sits at V/Q of <1 with average of ~0.8

Approximately 3.0

Approximately 0.6

Average V/Q of lung tissue is ~0/8 - This can be changed due to variation in one of the variables:

• R-L shunt = Pulmonary odema > some alveoli unventilated > portion of the blood from R heart doesnt get oxygenated by lung —> V=0 > V/Q = 0

  • PACO2 and PAO2 in the alveoli stabilises to venous BP (PA=PV) —> PACO2 increase from 5 to 6kPA, PAO2 decreases from 13 to 5kPa.

• Lack of perfusion = PE > lack of blood supply to part of lung > Q=0 > V/Q = ∞.

  • Here PACO2 and PAO2 stablises to pressure in inspired air (PA=Pi) —> PACO2 decreases from 5 to 0kPa, PAO2 increases from 13 to 20kPA.

Between these two extremes, increase in V/Q leads to:

• Decrease in PACO2 towards 0 kPa.

• Increase in PAO2 towards 20 kPa.

Decrease in V/Q leads to:

• Increase in PACO2 towards 6 kPa.

• Decrease in PAO2 towards 5 kPa.

Deoxygenated blood entering systemic circulation without being oxygenated in the lungs

• By giving IV radioactive material e.g. Xe133 then using radiation counters to calculate blood flow to different parts of the lungs

• Blood from heart > tricuspid valve > pulmonary artery > lung. Has pressure of ~20cmH2O (low compared to systemic circulation)

  • Moving upwards blood loses the pressure so 20cm above the tricuspid valve its 0, BP increase moving downwards = blood arriving to bases (below the valve level) has higher Pa & blood going to apex has low Pa

• As blood moves from artery > pulmonary capillaries > pulmonary vein, pressure drops. = Pv at a given vertical level is lower than Pa

• The difference between the Pv and Pa at the same vertical level remains constant = this is the driving force and is ~10cmH2O.

• At a higher region of the lung, Pv is negative

Lung tissue can be divided into 3 perfusion zones:

Zone 1

• Alveolar pressure > arterial > venous (PA>Pa>PV). - doesn’t exist in normal physiology.

• Here, no blood flow due to alveolar pressure being higher than arterial pressure > collapsed arterioles

Zone 2

• Arterial pressure > alveolar > venous (Pa>PA>PV) - Pv os sub-zero. The flow depends on the difference between Pa & PA = flow inc moving downwards as Pa increases

Zone 3

• Arterial pressure > venous > alveolar (Pa>PV>PA). This zone has the greatest blood flow. Alveolar pressure is irrelevant in this zone

• In zone 2, blood flow increases significantly moving vertically down the lungs - as Pa increases, Pa-PA difference increases.

• Increased arterial pressure > opening of arterioles = Recruitment of arterioles

• Blood flow to zone 3 relies on Pa-Pv difference - which remains constant.

• Moving down the lung, Pa increases so all the arterioles are already open (so ‘recruitment’ doesn’t occur) > ‘distension’ of blood vessels > slight increase blood flow.

PAO₂ decreases to ~5 kPa and PACO₂ increases to ~6 kPa

• This occurs due to R-L caused by unventilated alveoli due to pumonary oedema. V=0 so V/Q = 0

• Here, PACO2 and PAO2 in the alveoli stabilise to the pressures in the venous blood reaching the alveoli (PA = PV).

PAO₂ increases toward ~20 kPa and PACO₂ decreases toward ~0 kPa

• This happens due to lack of perfusion due to lack of blood supply to portion of the lung due to PE.

• Here Q=0 so V/Q = ∞

Pulmonary embolism

Zone 3

• Due to ‘distension’ of the already opened arterioles

Pa > Pv > PA

Decreased arterial pressure Pa (e.g., haemorrhage) or increased alveolar pressure PA (e.g., positive pressure ventilation)

• Zone 1 doesn’t exist in normal physiology - but it can arise in tissues which are normally in zone 2

• If either or both of decreased Pa / increased PA happens > no blood flow to apex of the lung as Pa is lower than PA

If V/Q ratio in a certain region inc or dec due to e.g PE or pulmonary oedema, the system initiates reflexes to restore it

-> If V/Q elevated e.g PE

• lead to increased local PAO2 & reduced PACO2

• System tries to reduce V/Q by:

  • Increase Q -> done by vasodilation.

    Decreased V -> by bronchoconstriction.

-> If V/Q reduced e.g. pulmonary oedema

• Lead to low PAO2 (hypoxia) and hypercapnia

• System tries to inc V/Q by:

  • Q decreased -> done by vasoconstriction.

  • V increased -> done by bronchodilation.

Constriction of pulmonary arterioles in response to hypoxia

• During hypoxia due to reduced V/Q, vasoconstriction reflex is initiated

• Blood flow reduced to restore V/Q and to divert blood away from poorly ventilated area of the lung to better area.

• The vasoconstriction in response to hypoxia is unique to pulmonary arterioles and is known as HPV

It causes vasoconstriction to reduce blood flow to the poorly ventilated area of the lung and divert it to the better ventilated area.

• This effect is unique only to pulmonary arterioles - in other arterioles of the body, hypoxia would lead to vasodilation in order to receive more blood.

1. Hypoxia inhibits exit of K+ ions from smooth muscle cells of blood vessels (via K+ channels)

2. This leads to membrane depolarisation.

3. Voltage-gated Ca2+ channels open, causing influx of Ca2+.

4. This initiates smooth muscle contraction -> vasoconstriction.

• In a healthy individual, ventilation and perfusion is matched = area highly ventilated receives good perfusion vice versa

• In pt with bronchitis/COPD - an affected, poorly ventilated area receives lots of blood flow. As ventilation is almost 0, V/Q is low > functional shunt > hypoxia & SOB > inc RR

• healthy area of the lung will have inc ventilation due to inc RR > high V/Q which compensates for area of low V/Q > normalises PaCO2

If a low PaO2/hypoxemia (arterial oxygen) was caused ONLY by hypoventilation, the A-a gradient would be normal.

The lower airways (bronchi, bronchioles, and alveoli)

Inflammation

Less than 0.7

≥12% and >200 mL increase

Greater than 20%

Airway hyperresponsiveness (suggestive of asthma)

FEV1

It is normal or increased

It is reduced

GOLD classification

No, it is not fully reversible

Chronic bronchitis and emphysema

Tobacco smoking

Alpha-1 antitrypsin deficiency

Th2 lymphocytes, eosinophils, and mast cells

Neutrophils, macrophages, monocytes, and CD8 lymphocytes