Respiratory

Physiology

  • The primary function of the lungs is to oxygenate blood. With a functioning circulatory system, haemoglobin as an oxygen carrier this should enable atmospheric or medically supplemented oxygen to get to all of the cells of the body and their mitochondria.
  • Mitochondrial oxidative phosphorylation will cease when PO2 falls below 1 mmHg (0.13 Kpa). A constant supply of oxygen allows the process of oxidative phosphorylation and Kreb's cycle with oxygen transport system to generate ATP. Byproducts are CO2 and H20. CO2 requires excretion.
  • Normal respiration rate is 15/minute. Expiration takes more time than inspiration in a ratio of 2:1. The ease at which a lung expands is the compliance - this is low with LVF, ARDS, Pneumonia. The lungs are stiff. Airway resistance = pressure gradient from mouth to alveolus divided by rate of flow - this is high with Asthma, COPD.
  • Inspiration whereby air is sucked in due to a negative intrathoracic pressure due to muscle contractions increasing thoracic volume happens by contraction of the diaphragm downwards becoming flatter (phrenic nerve C3/4/5) and contraction of external intercostals pulling ribs up and outwards and the occasional use of Accessory muscles - scalenes, sternocleidomastoids, pectoralis major, trapezius
  • These actions increase thoracic volume which creates negative intrathoracic pressure such that air moves along the pressure gradient inward, enters through both nostrils. Air enters the nose where the rich vascular supply warms it and is humidified and filtered. Air then passes via nasopharynx down across the larynx and into the trachea
  • In positive pressure ventilated patients air is pushed against a pressure gradient into the lungs as respiratory muscles are paralysed. Air entry is through an endotracheal tube or with non Invasive ventilation - a tight fitting face mask/nose. This creates a positive intrathoracic pressure which may be continuous or intermittent. Positive airways pressure can increase risk of lung trauma and pneumothorax.
  • Negative pressure ventilation is of historical interest - the "Iron lung" invented mainly to manage patients with polio related chest muscle weakness. Patients lay inside sealed compartment. Driven often by medical students who powered a pump which created a negative pressure within the sealed apparatus. It was this development that stimulated the whole development of ITU medicine and ventilation
  • Expiration unlike inspiration is largely passive using the relaxation of diaphragm and elasticity of lung tissue. Active expiration can be aided by internal oblique, external oblique, rectus abdominis, transversus abdominis

Pulmonary perfusion

  • The lung has a dual blood supply from bronchial vessels at 120/80 mmHg and Pulmonary vessels at 25/10 mmHg.
  • The pulmonary circulation is a low resistance network. Less power needed so RV is thin walled
  • Hypoxia causes localised hypoxic vasoconstriction within the pulmonary vascular bed.
  • Areas of low pO2 have low pulmonary blood flow and this diverts blood to areas of higher pO2.
  • The lung vascular system acts to oxygenate blood and excrete CO2, it filters out microthrombi returning from systemic circulation and converts Angiotensin I to angiotensin II. The lungs also act as a blood reservoir - increased with inspiration. Oxygenated blood returning to the heart in the pulmonary vein also gets some deoxygenated bronchial vein blood. The Left ventricle receives deoxygenated coronary blood via the thebesian veins
  • Successful oxygenation requires matching ventilation with perfusion. If areas are perfused but get no oxygen this is a shunt and leads to deoxygenated blood entering the left atrium.
  • No matter how much additional oxygen is given it will not restore full oxygenation with a shunt. This may be seen in pneumonia and consolidation or atelectasis or cyanotic congenital heart diseases.
  • In pulmonary embolism there is oxygenation but not perfusion.
  • Ventilation perfusion mismatching can be estimated by an increase in the Alveolar-arterial pO2 gradient which is normally < 2 KPa

Alveolus/capillary/erythrocyte interface

The surface area available for gas exchange is 90 m2 divided between 300 million alveoli of less than 1/5th of a mm in diameter in two lungs. The gases must traverse a distance of about 0.4 um.
  • Alveolar epithelium
  • Basement membrane of alveolus
  • Basement membrane vascular endothelial cell
  • Oxygen passes from high oxygen tension alveoli to low oxygen tension venous blood. CO2 passes from high tension venous side to low tension alveolus side. Both gases pass either way from alveolar air across alveolar epithelium basement membrane and capillary endothelium. Oxygen binds erythrocyte Haemoglobin and a small volume of oxygen dissolves in blood but most is carried bound to Hb. Haemoglobin bound oxygen carriage is determined by O2 dissociation curve.
  • Type 1 pneumocytes line the alveoli forming a thin layer allowing gaseous exchange. They are devoid of most organelles. Type 2 Pneumocytes secrete surfactant and some also become Type 1 pneumocytes. They have larger nuclei and microvilli and cytoplasm containing storage vesicles for surfactant release.
  • Surfactant is composed of phospholipids including sphingomyelin and lecithin. The molecules have a hydrophobic and hydrophilic end and so surfactant reduces alveolar collapse and improves alveolar stability. Surfactant lines the alveoli and lowers surface tension and allows easier inflation and deflation of the lungs. A loss of surfactant causes stiff lungs - neonates

O2 dissociation curve

  • The oxygen haemoglobin dissociation curve is sigmoidal and not a straight line. At low oxygen tension binding is poor and Hb releases oxygen to surrounding hypoxic tissues - enhances oxygen delivery where it is needed.
  • Hb is more "sticky" for oxygen when in high oxygen tension area and is good at binding oxygen when there is plenty such as in the lungs and giving it away when there is none.
  • These properties are affected by certain environmental factors and changes also in Hb. The steep middle section means that when there is a small drop in local PaO2 in the midzone there is a large release of oxygen

Oxygen delivery

  • Room air contains 21% oxygen. Small increases in arterial pO2 can cause significant improvements in oxygen carriage and delivery.
  • Nasal cannula can deliver 24-40% depends on flow rate. Simple face masks variable FiO2 depending on flow and respiratory rate
  • Venturi mask - uses venturi effect to mix air and oxygen to a more accurate concentration. Recommended in COPD
  • Non rebreather - used to give very high FiO2 where COPD is not an issue
  • Haemoglobin

    • Haemoglobin is composed of four subunits of Haem + globin each of which binds an O2 molecule at differing strengths giving rise to the sigmoidal curve.
    • A process called Cooperative binding. Anaemia makes the curve move vertically down and reduces oxygen delivery.
    • Polycythaemia makes the curve move vertically up improving O2 delivery as seen with "altitude training".
    • Anaemia becomes very significant in terms of oxygen delivery when Hb < 7g/dl.
    • Hb hold onto to O2 tighter (Leftward shift) when there is a
      • low PCO2, alkalosis
      • Low temperature, reduced 2,3 DPG
      • Carbon monoxide (binds to HbO2 sites avidly forming COHb and actually increases O2 affinity worsening tissue hypoxia )
      • Fetal Hb - has to remove oxygen from maternal Hb
    • Markers of metabolism makes Hb release O2 more easily "Delivery" (Right shift) such as
      • Raised PCO2, Acidosis
      • Raised temperature
      • Increased 2,3 DPG and Hb Kansas and some other abnormal Hb

    Respiratory control

    • Respiratory control is under control from central chemoreceptors in the ventral medulla which respond to increasing pCO2 indirectly by detecting increased CSF [H+] and stimulates the inspiratory centre causing increased rate and depth of respiration.
    • It may be affected by sedation, drugs, sleep, alcohol. There are also peripheral chemoreceptors in the carotid body (IX cranial nerve) and Aortic arch (X cranial nerve) which detect low pO2 primarily but also raised pCO2 and [H+] and also stimulates the inspiratory centre - increased rate and depth of respiration
    • The sensation of dyspnoea comes from afferent receptors in respiratory muscles such as juxtacapillary J receptors in lung sense interstitial oedema and chemoreceptors sensing hypoxia and hypercarbia
    • Normally pCO2 is the main gas that determines respiratory rate and depth. When the PO2 < 8Kpa hypoxia along with hypercarbia and acidosis drives the response.
    • In those with chronic raised CO2 its affect is reduced and hypoxia is the main driver of respiration. Giving excess oxygen can result in reduced respiratory effort and loss of hypoxic drive.

    Causes of hypoxia

  • Lung gets 4-6 L/min of air and 5L/min blood. Ventilation/perfusion ratio = 0.8 (4/5)
  • Lung apices V > Q so ratio > 0.8. Lung bases V < Q so ration < 0.8
  • Pulmonary embolism Q falls . V >> Q and so there is a VQ mismatch as aerated lung is under perfused "dead space"
  • Asthma/Pneumonia V falls. V < Q and there is a VQ mismatch as perfused lung is not aerated "shunt"
  • Physics of Respiration

  • Dalton's law - for 2 individual unreactive gases the total pressure exerted is the pressure of the first plus the second
  • Normal atmospheric pressure at sea level is 760 mmHg = 101 kPa. Air contains 21% oxygen and 78% nitrogen and 1% inert gases
  • Partial pressure of oxygen at sea level - Fraction in inspired air x atmospheric pressure = 0.21 x 760 = 159 mmHg = 21.2 Kpa
  • Partial pressure of oxygen On summit of Everest - Fraction in inspired air x atmospheric pressure = 0.21 x 252 = 52 mmHg = 6.9 Kpa so high FiO2 must be given