Physiology

The decrease in the oxygen affinity of haemoglobin in the presence of low pH or high CO2

"The Haldane effect is a physicochemical phenomenon which describes the increased capacity of blood to carry CO2 under conditions of decreased haemoglobin saturation"

• Sensors: pressure (carotid sinus and aortic arch)

• Afferent: vagus and glossopharyngeal nerves

• Processor: nucleus of the solitary tract and nucleus ambiguus

• Efferent: vagus nerve and sympathetic chain

• Effect: increased HR and BP in response to a fall in BP

• Afferent: vagus (atrial stretch) 

• Processor: nucleus of the solitary tract and the caudal ventral medulla

• Efferent: vagus nerve and sympathetic chain

• Effect: increased RA pressure produces an increased heart rate;

• Afferent: carotid / aortic chemoreceptors (low PaO2 and/or high PaCO2)

• Processor: nucleus of the solitary tract and nucleus ambiguus

• Efferent: vagus nerve and sympathetic chain

• Effect: bradycardia and hypertension in response to hypoxia (also secondary tachycardia from Bainbridge and Hering-Breuer reflexes)

• Afferent: mechanosensors in the rostral medulla?

• Processor: rostral ventrolateral medulla

• Efferent: sympathetic fibres to the heart and peripheral smooth muscle

• Effect: hypertension and baroreflex-mediated bradycardia

• Afferent: vagus (mechanical/chemical sttimuli to the cardiac chambers)

• Processor: nucleus of the solitary tract

• Efferent: vagus nerve and sympathetic chain

• Effect: hypotension and bradycardia in response to atrial stimulation

• Afferent: trigeminal nerve (pressure to the globe of the eye) 

• Processor: sensory nucleus of CN V; nucleus of the solitary tract

• Efferent: vagus nerve and sympathetic chain

• Effect: vagal bradycardia, systemic vasoconstriction, cerebral vasodilation

• Afferent: trigeminal nerve (cold temperature; pressure of immersion)

• Processor: sensory nucleus of CN V; nucleus of the solitary tract

• Efferent: vagus nerve and sympathetic chain

• Effect: vagal bradycardia, systemic vasoconstriction, cerebral vasodilation

• Afferent: emotional distress, hypovolaemia

• Processor: unknown

• Efferent: vagus nerve and sympathetic chain

• Effect: bradycardia, systemic vasodilation, hypotension

• Afferent: central respiratory pacemaker

• Processor: nucleus ambiguus

• Efferent: vagus nerve, via the cardiac ganglion

• Effect: cyclical increase of heart rate during inspiration

• Hypertension

• Bradycardia

• Irregular respiration

• periphere Chemorezeptoren: Es handelt sich um Glomuszellen, die als Gefäßknäuel über Seitenäste von benachbarten großen Arterien versorgt werden. Sie gehören im Verhältnis zu ihrer Masse zu den am besten durchbluteten Organen (ca. 20ml/min*g; vgl. Gehirn ca. 0,8 ml/min*g). Man unterscheidet Typ-I und Typ-II Glomuszellen. Sie befinden sich bilateral an der Teilungsstelle (Bifurkation) der Arteria carotis communisim Glomus caroticum und in der Aorta im Glomus aorticum - von dort ziehen sie bis in die Arteria subclavia dextra.

• Sie registrieren den arteriellen Sauerstoffpartialdruck(paO2) und können so eine Hypoxie erfassen. Die Informationen werden als Impulse über den Nervus vagus und den Nervus glossopharyngeus an das Atemzentrumweitergegeben.

• Azidose/erhöhtes CO2/H +Ionen/Hypoperfusion/Hyperthermie/ CO steigern Ventilation

  
  

• zentrale Chemorezeptoren: Sie liegen im Atemzentrum der Medulla oblongata des ZNS und messen den Kohlendioxidpartialdruck (paCO2), registrieren jedoch keine Hypoxie. Zudem werden sie durch einen Abfall des pH-Wertes im Liquor stimuliert.[1] h+Ionen

• Ventrolaterale Medulla

• Innerhalb der Bluthirn Schranke

• Respiratory system resistance is mainly a combination of resistance to gas flow in the airways and resistance to deformation of tissues of both the lung and chest wall.

• It is usually expressed as a change in pressure per unit flow, usually in cmH2O per litre per second. 

• Its reciprocal is conductance. Normally, specific airway conductance is used, which is conductance expressed per unit of lung volume.

• The total resistance of the respiratory system is composed of several contributing factors:

  • Resistance from deformation of the tissues (important at all flow rates)

    • Tissue resistance from lung parenchyma (~70%)

    • Tissue resistance from chest wall (~30% )

  • Inertance of air and thoracic tissues (important at high respiratory rates) 

  • Compression of intrathoracic gas (important mainly with high respiratory pressures)

  • Resistance from air flow friction, which in turn depends on

    • Reynolds number, which depends on

      • Airway diameter (increases with lung volume)

      • Airway length (increases with lung volume)

      • Flow rate

      • Gas density

      • Gas viscosity

    • Proportion of turbulent flow (at high flow, upper airways)

    • Proportion of laminar flow (low flow rates and in the lower airways)

• In normal airways, the flow is mainly laminar (turbulent flow is localised to the upper airways)

• Resistance to laminar flow increases in proportion to flow rate and is described by the Hagen-Poiseuilee equation, being affected by the following factors:

  • Airway length

  • The fourth power of airway diameter

  • Gas viscosity

• Resistance to turbulent flow increases exponentially with flow rate, and the main determinant of the rate of pressure change is the density of the gas.

Factors which affect airway resistance

• Gas properties which affect the type of flow

  • Gas density (increased density leads to increased turbulence and hence increased resistance)

  • Gas viscosity (increased viscosity promotes laminar flow and hence decreases resistance)

• Factors which affect airway diameter

  • Lung volume (resistance decreases with higher volume)

  • Physiological variation in airway diameter

  • Pathological conditions which affect airway diameter:

    • Mechanical obstruction or compression

      • Extrinsic, eg. by tumour

      • Dynamic compression, eg. due to gas trapping or forceful expiratory effort

      • Artificial airways and their complications, eg. endotracheal tube becoming kinked 

    • Decreased internal crossection

      • Oedema

      • Mucosal or smooth muscle hypertrophy

      • Encrusted secretions

    • Decreased smooth muscle tone

      • Bronchodilators

      • Sympathetic nervous system agonists

    • Increased smooth muscle tone

      • Bronchospasm

      • Irritants, eg. histamine

      • Parasympathetic nervous system agonists

• Factors which affect airway length

  • Lung volume (increasing volume stretches and elongates the bronchi)

  • Artificial airways  (increase the length in the case of an ETT, or decrease it in the case of a tracheostomy)

• Factors which affect flow rate

  • Respiratory rate (increased respiratory rate produces an increase in the flow rate for each breath) 

  • Inspiratory and expiratory work (eg. voluntary forced expiration for spirometry)

  • Inspiratory flow pattern generated by a mechanical ventilator

Other factors which affect respiratory resistance as a whole:

• Resistance from deformation of the tissues (important at all flow rates)

  • Tissue resistance from lung parenchyma (~70%)

  • Tissue resistance from chest wall (~30% )

• Inertance of air and thoracic tissues (important at high respiratory rates) 

• Compression of intrathoracic gas (important mainly with high respiratory pressures)

• Pulmonary blood flow:

  • Increased blood flow results in decreases pulmonary vascular resistance in order for pulmonary arterial pressure to remain stable

  • This is due to: 

    • Distension of pulmonary capillaries (mainly), and

    • Recruitment of previously collapsed or narrowed capillaries

• Lung volume:

  • Relationship between lung volume and PVR is "U"-shaped

  • Pulmonary vascular resistance is lowest at FRC

  • At low lung volumes, it increases due to the compression of

  • larger vessels

  • At high lung volumes, it increases due to the compression of small vessels

• Hypoxic pulmonary vasoconstriction

  • A biphasic process (rapid immediate vasoconstriction over minutes, then a gradual increase in resistance over hours)

  • Mainly due to the constriction of small distal pulmonary arteries

  • HPV is attenuated by:

    • Sepsis and pneumonia

    • hypothermia

    • iron infusion

• Metabolic and endocrine factors:

  • Catecholamines, arachidonic acid metabolites (eg. thromboxane A2) and histamine increase PVR

  • Hypercapnia and (independently) acidaemia also increase pVR

  • Alkalaemia decreases PVR and suppresses hypoxic pulmonary vasoconstriction

  • Hypothermia increases PVR and suppresses hypoxic pulmonary vasoconstriction

• Autonomic nervous system:

  • α1 receptors: vasoconstriction

  • β2 receptors: vasodilation

  • Muscarinic M3 receptors: vasodilation

• Blood viscosity

  • PVR increases with increasing haematocrit

• Drug effects:

  • Pulmonary vasoconstrictors: Adrenaline, noradrenaline and adenosine

  • Pulmonary vasodilators: Nitric oxide, milrinone, levosimendan, sildenafil, vasopressin, bosantan / ambrisantan, prostacycline and its analogs, calcium channel blockers and ACE-inhibitors.

cAMP

cAMP Vasodilatator in der Lunge

cGMP vasodilatativ durch Calcium

• Global ventilation of the lungs is expressed as the minute volume , normally around 4L/min

  • This is affected by multiple factors, most notably pregnancy, PaCO2, PaO2, pH, body temperature, exercise and blood pressure 

• Global perfusion  of the lungs is directly proportional to the cardiac output (normally 5L/min)

  • Therefore, this is affected by all the factors which affect cardiac output, which include exercise, metabolic rate, volume-sensing reflexes, autonomic tone, etc.

  • The global perfusion of the lungs is approximately 5L/min at rest

• Global V/Q mismatch occurs when:

  • there is signficantly reduced ventilation with intact perfusion (shunt)

  • there is reduced perfusion  (increased physiological dead space)

• Regional differences in perfusion and ventilation develop because: 

  • The global perfusion of the lungs occurs at a low pressure, which means that the hydrostatic pressure of the column of blood blood therefore has a significant influence.

  • Lung ventilation occurs predominantly because of the changes in the shape of the thoracic cavity which occur unevenly (i.e. the base expands more than the apex)

  • Regional changes in pulmonary arterial resistance (eg. due to atelectasis and hypoxic vasoconstriction) change the distribution of blood flow in response to the distribution of ventilation

• Regional differences in perfusion and ventilation are affected by:

  • Posture and gravity (which affects the pressure in the hydrostatic column)

  • Factors which affect regional pulmonary blood flow:

    • Lung volume (atelectasis increases pulmonary vascular resistance)

    • Hypoxic pulmonary vasoconstriction

    • Gravity (affects the direction of the hydrostatic gradient)

    • Pulmonary vascular architecture (some lung units are structurally advantaged)

  • Factors which affect regional ventilation:

    • Gravity (the weight of the lung) which produces a vertical gradient in pleural pressure

    • Posture, which changes the direction of this vertical gradient

    • Anatomical expansion ptential (i.e. bases have more room to expand than apices)

    • Lung compliance (more compliant lung regions, eg. lung bases, will be better ventilated at any given traspulmonary pressure

    • Pattern of breathing

• The lung can be divided into discrete regions according to the interplay between alveolar pressure, arterial pressure and venous pressure.

• These regions are:

  • Zone 1, where alveolar pressure is higher than arterial or venous pressure;

  • Zone 2, where the alveolar pressure  is lower than the arterial but higher than the venous pressure

  • Zone 3, where both arterial and venous pressure is higher than alveolar

  • Zone 4, where the interstitial pressure is higher than alveolar and pulmonary venous pressure (but not pulmonary arterial pressure)

• Under normal circumstances, Zone 1 (a poorly perfused region containing a lot of dead space) does not exist, and only manifests in certain scenarios:

  • Positive pressure ventilation

  • Hypovolaemia, eg. haemorrhage

• Trap for airborne particles:  generally, nothing larger than 2.5μm gets to the alveoli

• Reservoir of blood: the lungs contain about 10% of the circulating blood volume

• Route of drug administration (eg. nebulised steroids and bronchodilators)

• Route of drug elimination  (eg. volatile anaesthetics)

• Metabolism (eg. conversion of of angiotensin-I, and degradation of neutrophil elastase by α1-antitrypsin)

• Modulator of acid-base balance by virtue of CO2 elimination

• Modulator of the clotting cascade: the lungs contain thromboplastin, heparin and tissue plasminogen activator

• Filter for the bloodstream: particles larger than an RBC are trapped (~8  μm size barrier), which includes clots, tumour cells and other emboli

• Antimicrobial and immune functions: Alveolar macrophages and sequestered neutrophils, mast cells in the lung and bronchi, immunoglobulin in the respiratory mucus (IgA)

• Modulation of body temperature: heat loss can occur by respiration

• Organ of speech: the lungs form a part of the system which permits communication by sound and language