L2: Airway resistance, pulmonary circulation, fluid movement

Resistance within the respiratory system

• change in pressure per unit flow

  • in cmH2O per litre per second

Resistance of respiratory system comes from a combination of factors

• Main one→ resistance from air flow friction

Airway resistance (R)

• the force that impedes airflow along the respiratory passages

Airway resistance is primarily affected by

1. airway diameter→ (resistance greater in narrower airways)

2. If there is turbulent or laminar air flow

   • resistance greater with turbulent flow

Type of flow in respiratory tres

1. Turbulent air flow

2. Laminar air flow

3. Transitional flow

1. Turbulent air flow

• WHERE occurs in the large airways 

  • trachea and the large bronchi→ especially at high flow rates

• WHAT air flows in disorganised patterns

  • sounds that can be heard when breathing deeply

    • under stethoscope during normal respiration

2. Laminar flow

• WHAT streamlined flow of air that runs parallel to the sides of the airways

  • silent

• WHERE: small airways

  • where flow is very slow

3. Transitional flow

• WHAT: mix between the two

• WHERE: mostly in lower airways of the lung

  • where conditions for true laminar flow (essentially flow through long straight tubes) are not met

How does turbulent flow affect resistance?

• creates greater resistance to flow

Airway diameter:

Importance of the tube diameter to resistance:

• Small reductions in radius→

  • dramatically increase the resistance 

  • → reduce flow

    • (unless grater work is applied to generate a steeper pressure gradient)

Under normal respiratory conditions…

• air flows through the respiratory passageways easily

• as little as 1 cmH2O pressure gradient is sufficient for eupnea

Where is the greatest resistance to air flow?

Upper respiratory tract:

• although the airways are larger there are fewer of them

Why is this counterintuitive

• Tiny bronchioles have smaller individual diameter

  • but so many of them→ tiny amounts of air must flow through each

  • → resistance is low

Dynamic control of Airway Resistance: how can bronchioles be dynamic

• have muscular walls

  • contract to restrict air→ flow regionally or across the whole lung

Why is it useful that they are so small?

• so narrow so small changes in diameter or accumulation of mucus

  • within them→ can have dramatic effects on air flow through the lung

Dynamic effects of the lungs

1. Regional bronchiole constriction: 

   • help maintain a normal ventilation:perfusion ratio

   • WHEN:constriction occurs in regions of poor perfusion

2. Dilation of bronchioles: 

   • WHEN: response to sympathetic stimulation

   • Sympathetic innervation→ only modest 

   • Sympathetic stimulation by circulating adrenaline and noradrenaline→ stimulate  beta-adrenergic receptors cause marked dilation  of the bronchial tree

3. Constriction of bronchioles

   • WHEN: in response to parasympathetic stimulation by the vagus nerve

     • ALSO: stimulated by local reflexes→ triggered by noxious stimuli

       • gases or infection

4. Histamine release by mast cells

   • or as part of systemic allergic reaction

   • → causes bronchoconstriction

Asthma

1. abnormal degrees of airway narrowing

• seen in allergic airway diseases

• Inflammation→ causes swelling around the airways 

• Mucus→ accumulation in the airways

OVERALL: Narrowing the airways

2. Airways Hyper-reactive 

   • prone to bronchoconstriction when exposed to minor insults like cold air

What is bronchoconstriction perpetuated by

• histamine release from mast cells

  • involved in allergy

Dynamic pressure changes also affect airway resistance

• on top of pressure-volume changes during the respiraotry cycle

  • in terms of the lung parenchyma and alveolar expansion

• BUT also airways also experience pressure changes

The diameter of airways with lung volume changes:

• the lungs expand the connective tissues

• this suspends the airways within the lung parenchyma pull outwards and expand the airway diameter

What happens at respiration at rest (eupnoea)

1. Alveolar pressures fluctuate from -2 to +2 cmH2O at most

2. Pleural pressures are always negative

   • Tend to hold alveoli and airways within the thoracic cavity open

Airway collapse during expiration: what happens during forced expiration

• intrathoracic pressures become large and position 

  • → with important implications

Forced expiration

• see a trace when a patient inspires to total lung capacity

  • then maximally exhales as far as possible→ to residual volume

Break down of what happens

1. A→ subject exhales as fast as they can

2. B→ exhales more slowly

3. C→ exhale slowly to begin→ then maximally (at the inflection point)

Result of this

• Peak flow depends on the force of expiration

• BUT

• below a given volume, the rate of flow drops and is effort independent

→ However hard you try: it is impossible to increase flow

The reason for this?

• below a given volume, the pressures within the thorax are such that small airways collapse 

• → reducing the maximal rate of flow

Just as there is transmural pressure on the alveolus→ (intra-alveolar pressure-pleural pressure)

… there is a trans-airway pressure (airway pressure-pleural pressure)

Pressures during different parts of the cycle

1. During inspiration→ large negative pleural pressure tends to keep airway open

   • trans-airway pressure large and positive

2. At end of inspiration→ pressure within the airway and alveolous equilibrates with atmospheric pressure

   • and the trans airway pressure remain large and positive

3. During forced expiration→ pleural pressure can be very large and positive

   • elastic recoil of the lung parenchyma ensures that the alveolar pressure are even more positive

   • so trans airway pressure remains large and positive

However, as you get further from the alveolus→

• the lower the airway pressure is

WHY: airway resistance means the airway pressure reduces gradually along the distance from alveolus to mouth

Due to the decrease in airway pressure…

• at some point up the respiratory tree→ the trans-airway pressure (=airway pressure- pleural pressure) will become zero

→ This is Equal pressure point EPP

Beyond this point…

• Becomes negative:

  • The force tending to collapse the airway

What happens when the equal pressure point EPP lies within the airways supported by cartilage?

→ no collapse will occur

But what happens when the equal pressure point EPP lies within the unsupported bronchioles

→ collapse will occur

Due to this narrowed  or sompletely collapsed airway…

Resistance:

• high

Outward air flow:

• stopped or limited

Even in healthy lungs, during forced expiration…

• some airways collapse

→ underlies the observation that even if you really try→ still limit to peak expiratory flow

Dynamic airway collapse is only influential during…

• forced expiration 

  • where pleural pressures get very high and positive

BUT: some lung pathologies can lead to problematic air trapping due to airway collapse

In conditions with high lung compliance (emphysema)

Elastic recoil of the alveoli is not great:

• Even if transmural pressure is positive to keep alveoli open

  • → airway pressures will also be lower

  • → equal pressure point moves lower in the respiratory tree

How low can the EPP move to

• can move so low that airway collapse occurs even during ‘normal’ breathing for that patient

• → leads to:

  1. air trapping

  2. positive pressure within the alveoli at the start of the next inspiration

  3. and lung hyperinflation

What do emphysema patients learn to do to reduce the slope of pressure gradients between alveoli and the outside

• learn to breathe out through pursed lips

OVERALL: preventing airway collapse by moving the EPP towards the mouth

What happens in conditions with increased airway resistance (asthma)

• pressure within the airways dissipates more rapidly

  • → leading:

    • to the EPP moving lower in the respiratory tree

    • having the potential to cause airway trapping

Extra-thoracic airway collapse during inspiration: What happens during rapid inspiration

• negative pressure within the airways tends to suck soft tissues towards the midline→ obstructing air flow

• Problems caused:

  • where structural or functional integrity is lost for some reason

The pulmonary circulation: the two distinct  circulations of the lungs

1. Bronchial circulation

2. Pulmonary circulation

1. Bronchial circulation

• received <2% of left side cardiac output

  • high pressure, low flow system

  • fed by bronchial arteries delivering oxygenated blood to the conducting airways

  • supporting structures of the lungs

• majority is drained into pulmonary circulation

  • causing a small drop in PO2 between blood leaving the alveoli full oxygenated and entering the left side of the heart

    • Coz of the venous admixture of deoxygenated blood from the bronchial circulation

2. Pulmonary circulation: pulmonary artery

1. receives blood from the right ventricle

2. arterial branches carry blood to the alveolar capillaries for gas exchange

3. pulmonary veins return the blood to the left atrium

4. to be pumped by the left ventricle through the systemic circulation

→ OVERALL: low-pressure high flow system

2. Pulmonary circulation: capillary bed MAIN FUNCTION

• places the blood in intimate contact with the alveoli

  • to facilitate rapid gas diffusion

2. Pulmonary circulation: capillary bed SECONDARY FUNCTIONS: blood reservoir

Blood reservoir→ 40% of weight is blood (approx 500m or 10% blood volume in human)

2. Pulmonary circulation: capillary bed SECONDARY FUNCTIONS: Filters the blood of emboli

eg: clots, fat globules or air

• would otherwise enter systemic circulation and blood blood flow to critical organs

• Emboli are trapped in small pulmonary arterioles and capillaries

• → pulmonary endothelial cells release fibrinolytic agents→ dissolve clots

• Air emboli can be harmlessly absorbed

issue with large emboli?

• can block blood flow to significant areas for the lung

  • → cause serious clinical signs and many small emboli

• many small emboli can also significantly compromise lung function

• infectious emboli can set up pulmonary abscesses

2. Pulmonary circulation: capillary bed SECONDARY FUNCTIONS: metabolises vasoactive hormones

• e.g Angiotensin I

• converted to angiotensin II→ by angiotensin converting enzyme

  • located on the cell surface  of the pulmonary endothelial cells

  • With 80% of Ang I converted to Ang II

  • during a single pass through the pulmonary vasculature

• Many other vasoactive hormones are metabolised in the lungs too

3. Pulmonary circulation: Lymphatics

• vessels present in all supportive strucutres of the lung

• mainly drain into the right thoracic lymph duct

3. Pulmonary circulation: Lymphatics→ particulate matter

1. gets as far as the alveoli 

2. partly removed in the lymph

   • → as plasma protein which may leak from lung capillaries

3. Which might otherwise exert osmotic pressure within the alveoli or interstitium

Differences between pulmonary and systemic circulations

1. Pul: carries entire output of the right side of the heart

   • syst: divided between different organs

2. Pul: blood enters the circulation deoxygenated and returns to the heart oxygenated

   1. syst: opposite is true of the systemic circulation

3. Pul: driving pressure and mean capillary pressure in pulmonary circulation is much lower than the systemic circulation

4. Pul: resistance is low compared to systemic

5. pul: vessels compliant

   • syst: vessels much less compliant

   • → coz there is less muscle in the walls in pulmonary vs systemic arteries

6. Pul: vessels respond to hypoxia with vasoconstriction

   • systemics ones→ by vasodilation

REMEMBER THESE DIFFERENCES

Resistance to flow in pulmonary vessels is …

• generally low

Cardiac output is driven through the lungs with a pressure gradient of

• only approximatley 10 mmHG

in contrast:

• pressure gradient for the movement of the same volume of blood in the systemic circulation is 85-90 mmHg

The resistance of the pulmonary circulation compared to the systemic vascular resistance

• 1/10th of the systemic vascular resistance

How is this achieved?

1. enormous number of pulmonary vessles to accommodate flow → easily dilated

2. when cardiac output increases (e.g during exercise)→ pressure does not increase much

   • why?→ highly compliant vessels dilate (distension)

     • this reduces resistance within them

     • capillaries that were previously collapsed are recruited so increasing the capacity for blood flow

3. During intense exercise→ pulmonary capillary pressure rise

   • as high as 40mmHG in humans or 100 mmHg in racehorses

   • → damage the delicate alveoli and cause haemorrhage in extreme circumstances

Pulmonary vascular resistance also changes in response to hypoxia:

• Pulmonary vessels: vasoconstriction

• Systemics: vasodilatation

  • RESULT: in the lungs→ diverts blood away from poorly ventilated areas of lungs→ to better ventilated ones

  • THEREFORE: blood contributes more meaningfully to gas exchange

OVERALL: response is an effort to maintain optimum ventilation/perfusion ratio across the lung→ which is more shortly

Fluid exchange in the lungs: low pressure of the pulmonary vasculature also has implications for…

• movement of fluid in the lungs

  • → (which is susceptible to qualitatively similar but qunatitiatively different hydrostatic and osmotic pressures)

Net fluid exchange across the capillary is determined by…

• difference in hydrostatic and colloid osmotic pressure across the capillary wall

Compared to the lungs…

• we cannot stop at considering leakage of fluid from the capillary into the interstitium

• → ALSO potential for fluid to leak into the alveolus within the alveolus

  • and effect of surface tension within the alveolus

Forces tending to cause movement of fluid outward from the capillaries and into the pulmonary interstitium

Forces tending to cause absorption of fluid into the capillaries:

This net flow of fluid into the interstiatil space is drained…

• by the lympth system

Under normal circumstances, what happens to the interstitial fluid?

• does not enter the alveoli

Two factors that ensure this:

1. interstitial pressure is negative→ THUS pulling water away from the alveoli

2. Surfactant acts as a barrier to fluid movement that attempts to enter the alveoli via capillary action

However…

• this is a fine balance and susceptible to disruption

If filtration of fluid exceeds removal…

• oedema ensures

• → with filling of the interstitial spaces and alveoli with fluid

This can occur as a result of:

1. increase in pulmonary capillary pressure 

   • (e.g left side heart failure)

2. increase in pulmonary permeability

   • (e.g inflammation, mechanical damage due to overinflation, exposure to toxic gas)

3. Decreased capillary colloid osmotic pressure

   • (e.g hypoalbuminemia in some kidney diseases or starvation)

4. Increase in surface tension in alveoli

   • (e.g lack of surfactant in premature neonates)

5. Failure of lymphatic drainage

   • (e.g inflammation of lympthatics physical obstruction)