The Physiology of Respiration

1. The Physiology of Respiration 

2. Introduction prime function of the respiratory system is to facilitate transport of oxygen (O2) from the atmosphere into blood and the transport of carbon dioxide (CO2) from the blood into the atmosphere.

3. Why do we need to breathe? Breathing gets O2 into the body so that cells can make energy Cells use energy to contract muscles and power thousands of biochemical reactions taking place in cells every second Without O2 = cells can�t make energy - without energy= cells die

4. Inside cells, most energy is made by the mitochondria In the form of a small packet of energy called ATP (adenosine triphosphate) During energy production, glucose and lipids are broken down and their energy used to produce ATP O2 is consumed and CO2 is formed as a waste gas.

6. The anatomy of the Respiratory System The structure of the respiratory system allows transfer of air between the outside of the body and the respiratory membranes in the lungs - Site of gas exchange

8. A series of tubes= Trachea, Bronchi, to the smallest= bronchioles, transfer air from outside to the alveoli where gas exchange takes place millions of alveoli in each lung each surrounded by a network of capillaries

10. Respiratory Zone Gas exchange site= Smallest (terminal) bronchioles and alveoli Walls of alveoli single layer Type I cells (simple squamous) Type II cells Cuboidal Secrete surfactant Alveolar macrophages (dust cells)

11. The Pleura and Pleural Fluid The Pleural membranes: Parietal pleura � lines thoracic wall and diaphragm Visceral pleura � covers external lung surface Pleural Fluid Fills pleural cavity Lubricates Surface tension of pleural fluid prevents separation of pleura Prevents collapse Pleurisy � pleural surfaces become dry and rough which results in friction and stabbing pain with each breath. OR pleura can produce too much fluid which exerts pressure on the lungs. This hinders breathing but is less painful than dry type.Pleurisy � pleural surfaces become dry and rough which results in friction and stabbing pain with each breath. OR pleura can produce too much fluid which exerts pressure on the lungs. This hinders breathing but is less painful than dry type.

12. Airflow Airflow rate is dependant upon: Airway Resistance Magnitude of frictional interactions between flowing gas molecules Length of airway Radius of conducting airways Main determinant of resistance Pressure gradient Movement from high to low (i.e. diffusion)

14. Airway resistance In a healthy respiratory system airway resistance is low so main determinant of airflow rate is pressure gradient Changes in airway size are achieved by ANS depending upon the body�s needs Parasympathetic Occurs in quiet relaxed situations (rest & digest) Promotes bronchoconstriction Sympathetic Occurs during exercise / active situations (fight or flight) Promotes bronchodilation

15. Inspiration Can be quiet or forced Contraction of diaphragm and external intercostal muscles increase volume of thoracic cavity As thoracic cavity increases, lungs are stretched - pleura Intrapulmonary volume increases Results in a drop in intrapulmonary pressure Air will rush in until pressure is equal on both sides

16. Inspiration Deep (Forced) inspiration Occurs during Vigorous exercise COPD Capacity of lungs increased Involves other neck and chest muscles Sternocleidomastoid muscles Scalenes Pectoralis minor

17. Expiration Passive process diaphragm and external intercostal muscles relax decreases volume of thoracic cavity As thoracic cavity decreases, lungs recoil Intrapulmonary volume decreases Results in an increase in intrapulmonary pressure Causes gases to flow out of lungs

18. Forced expiration Active process (requires energy) Produced by contraction of abdominal wall muscles (most influential) and internal intercostal muscles Contractions: Increase intra-abdominal pressure by forcing abdominal organs against diaphragm Depresses rib cage

19. Ventilation Thus: Air enters and leaves lungs by changes in pressure gradients. pressure changes brought about by Volume changes Volume changes brought about by actions of respiratory muscles

21. Factors affecting pulmonary ventilation Airway resistance Elasticity Elastic recoil Connective tissue contains large amounts of elastin fibres Compliance Distensibility of lungs Compliant lung easily stretched, little pressure required to inflate lungs

22. Surface tension Alveolar surface tension displayed by thin liquid film that lines each alveolus At an air-water interface, water molecules are more strongly attracted to each other than to air molecules This produces a force known as surface tension Consequently an alveolus would: Resist being stretched Tend to reduce in size Tend to recoil after being stretched. Greater the surface tension the less compliant the lungs

23. Pulmonary surfactant If alveoli were lined with water alone lungs would collapse and i.e. poor compliance Type II alveolar cells secrete surfactant a phospholipoprotein which spreads between water molecules thereby reducing surface tension.

24. Causes of pulmonary surfactant deficiency

25. Work of breathing Energy expenditure during breathing depends upon: Rate and depth of ventilation Lung compliance Airway resistance

26. External (Pulmonary) Respiration PO2 of alveolar air is 13.3kPa/105mmHg PO2 of deoxygenated blood entering pulmonary capillaries is 5.3kPa/40mmHg. Consequently oxygen diffuses from alveoli into blood stream until equilibrium is reached at 13.3kPa PCO2 of deoxygenated blood is 6.1kPa, PCO2 of alveolar air is 5.3kPa. What will occur? Po2 of alveolar air is 105mmHg. Po2 of deoxygenated blood entering pulmonary capillaries is 40mmHg. Blood leaving the capillaries mixes with a small volume of blood through conducting passages where gaeous exchange has not ocurred.Po2 of alveolar air is 105mmHg. Po2 of deoxygenated blood entering pulmonary capillaries is 40mmHg. Blood leaving the capillaries mixes with a small volume of blood through conducting passages where gaeous exchange has not ocurred.

27. Internal (Tissue) Respiration PO2 in tissue cells is 5.3kPa PO2 of oxygenated blood entering pulmonary capillaries is 13.3kPa. Consequently oxygen diffuses from blood stream into cells until PO2 in blood declines to 5.3kPa PCO2 of oxygenated blood is 5.3kPa, PCO2 in tissue cells is 6.1kPa. What will occur?

28. Principles of gaseous exchange Daltons Law states: total pressure exerted by a mixture of gases = sum of pressures exerted by each gas in mixture. The pressure exerted by each gas (partial pressure= p) is directly proportional to its percentage in the total gas mixture. Related to blood gas partial pressures � pCO2 and pO2. Thus if concentration of oxygen in plasma decreases, pO2 decreases

29. Boyles law states: volume is inversely proportional to pressure - relevant to principles of ventilation. When intra-pulmonary volume increases = pressure decreases

30. Henrys Law states: when a mixture of gases is in contact with a liquid, each gas will dissolve in the liquid in proportion to its partial pressure This relates to gaseous exchange at alveolar / pulmonary capillary membrane.

31. Respiratory Control Centres Inspiratory centre in medulla oblongata Expiratory centre in medulla oblongata Apneustic centre in pons Pneumotaxic centre in pons

32. Control of Respiration The inspiratory centre in medulla sets breathing rhythm connected to diaphragm via phrenic nerves (III,IV,V cervical nerves) and to intercostal muscles via intercostal nerves (T1-12 thoracic nerves). Impulses stimulate contraction and inspiration follows When impulses cease, muscles relax and expiration occurs Cycle repeats approx. 12-15 times per minute (autorhythmic neurones).

33. Control of Respiration Expiration results from passive recoil of the lungs (& muscles) Neurones of expiratory centre (Ventral Respiratory Group) are inactive during quiet breathing but are activated during forced/laboured breathing Expiratory centre contains both inspiratory and expiratory neurones and is activated during forced breathing. =stimulates contraction of internal intercostals and abdominal muscles. Furthermore VRG increases inspiratory activity.

34. Control centres in the pons Pons exerts �fine tuning� influences over the medullary centres Pneumotaxic centre Switch off inspiratory neurones, thus limiting duration of inspiration Apneustic centre prevents inspiratory neurones from being switched off thus prolonging inspiration. Without pneumotaxic breathing patterns are prolonged inspiratory gasps interupted by very brief expirations � apneusis. If entire pons is destroyed a normal balance between inspiration and expiration occurs providing vagal input is intact.Without pneumotaxic breathing patterns are prolonged inspiratory gasps interupted by very brief expirations � apneusis. If entire pons is destroyed a normal balance between inspiration and expiration occurs providing vagal input is intact.

36. Factors affecting rate and depth of respiration Hering � Breuer reflex Stretch receptors in bronchi and bronchioles When stimulated, send impulses along vagus nerve to inspiration (Pneumotaxic?) centre Inspiration is inhibited and expiration occurs Prevents over inflation of lungs Higher brain � voluntary controlHigher brain � voluntary control

37. Factors affecting rate and depth of respiration Voluntary Control Control from cerebral cortex (breath-holding, speech etc.) Chemical regulation Central chemoreceptors in medulla sensitive to changes in H+ conc or PCO2 in CSF Peripheral chemoreceptors in aortic and carotid bodies are sensitive to changes in H+, PCO2 and PO2

38. ChemoreceptorsCO2 + H2O ? H2CO3 ? H+ + HCO3- H+ sensitive Central ( poor diffusion across BBB) Peripheral Carbon dioxide sensitive � powerful respiratory stimulant Peripheral Weakly sensitive to arterial pCO2 Central Very sensitive to H+ in CSF Oxygen sensitive Peripheral (carotid arteries and aortic arch) Stimulated when oxygen tension falls below 8kPa /90% sat Sensitive to pO2 � implications?

39. Gas transport

40. Oxygen transport Total oxygen content includes: Percentage dissolved � 2% Reflected by pO2 Amount of O2 dissolved in plasma = 0.23ml/litre/kPa Carriage by haemoglobin � 98% Reflected by SaO2 1g of Hb can carry 1.34ml of oxygen if fully saturated

41. Haemoglobin (Hb) Protein part � globulin � is composed of 4 polypeptide chains Each polypeptide chain has an iron containing haem group Oxygen binds to the haem group forming oxyhaemoglobin Each haemoglobin molecule can carry up to 4 units of oxygen Haemoglobin binding to oxygen is reversible

42. Haemoglobin

43. Haemoglobin

44. Oxygen dissociation curve The degree to which oxygen binds with Hb depends upon (PO2)(oxygen tension) � see oxygen dissociation curve The affinity of Hb for O2 is not constant The first molecule of oxygen binds with Hb with relative difficulty The second and third molecules have a greater affinity (as seen by the steepest part of the sigmoid curve) The fourth oxygen molecule binds with the greatest difficulty

45. Oxygen dissociation curve The sigmoid shape of the O2 curve is physiologically significant Oxygen diffuses into red blood cells at the lungs, then diffuses out at the site of the tissues The speed of loading and unloading of oxygen is dictated by partial pressure gradients

47. Partial pressure gradients � oxygen binding Blood arriving in the lungs has a low PO2 of 5.3kPa and is exposed to alveolar PO2 of 13.3kPa Oxygen diffuses down the gradient from alveoli into plasma This causes a rise in plasma PO2 enabling oxygen to diffuse into the red blood cells As PO2 increases from 5.3 to 8kPa in the red blood cells, there is rapid loading so Hb saturation reaches 90% ( steepest part of the curve) Thereafter O2 uptake declines until 97% is attached at 13.3kPa O2 This flat portion of the curve provides a safety barrier as even if PO2 falls to 8kPa as might occur in lung disease, 90% of Hb remains saturated

48. Partial pressure gradients � oxygen release As blood enters the tissues, still with a PO2 of 13.3kPa, it is exposed to PO2 of 5.3kPa so oxygen is readily released oxygen diffuses from the plasma into the tissues, causing a drop in plasma PO2 and thus HbO2 to dissociate Plasma PO2 remains relatively high, facilitating oxygen diffusion into the cells If tissue activity increases, Plasma PO2 may fall to 2kPa which allows Hb to release 80% of its oxygen Below PO2 of 1.3kPa myoglobin allows greater oxygen extraction from the blood

49. Factors affecting Hb affinity Factors reducing affinity Reduction in pH Increase in pCO2 Increase in temp Increase in 2,3-Diphosphoglycerate( produced during anaerobic glycolosis) Carbon monoxide (CO) Factors which increase affinity Increase in pH Reduction in pCO2 Reduction in temp Reduction in 2,3-DPG

51. Hypoxia Hypoxia indicates the situation where tissues are unable to undergo normal oxidative processes because of a failure in the supply or utilisation of oxygen. There are four categories of Hypoxia: Hypoxic hypoxia Anaemic hypoxia Stagnant (circulatory) hypoxia Histotoxic hypoxia

52. Hypoxic hypoxia Inadequate PO2 in arterial blood (PaO2). May results from: Inadequate PO2 in inspired air Major hypoventilation Inadequate alveolar � capillary transfer

53. Anaemic Hypoxia PaO2 normal but concentration of functional haemoglobin is reduced. Possible causes of anaemia: Deficiencies of iron, vitamin B12, folate or copper Kidney disease affecting production of erythropoietin Excessive blood loss Hereditary spherocytosis (RBCs have short life span) Carbon monoxide poisoning Iron reqiured for haem Others stop ed cells dividing so that fewer cells are produced.Iron reqiured for haem Others stop ed cells dividing so that fewer cells are produced.

54. Stagnant hypoxia Reduction in supply of oxygen to tissues produced by a reduced blood flow i.e. circulatory failure (e.g. angina, claudication etc.) PaO2 (and PaCO2) may be normal but delivery is not. Initially tissue oxygenation is maintained by increasing the degree of oxygen extraction from the blood, but as tissue perfusion worsens this becomes insufficient and tissue hypoxia occurs.

55. Histotoxic hypoxia Occurs when respiring cells are prevented from using oxygen= disabled oxidative phosphorylation enzymes Causes include: Cyanide poisoning Toxins produced by sepsis PaO2 is normal

56. Management of hypoxia Aim = maintain adequate perfusion pressure and oxygen delivery to ensure regional delivery. Reduce tissue oxygen demand by reducing metabolic rate. Achieved by: Respiratory support Oxygen therapy Non invasive or mechanical ventilation Cardiovascular support Optimise preload Reduce afterload Increase contractility Increase HR Maintain Hb within normal levels if needed Need to discuss the rationale of such treatments . Also advantages and disadvantagesNeed to discuss the rationale of such treatments . Also advantages and disadvantages

57. Transport of CO2 Three methods of transport Dissolved in plasma (PCO2) � approx 7% Binds to haemoglobin to form carbaminohaemoglobin � approx 23% Majority travels as bicarbonate ion HCO3- - approx 70%

58. CO2 transport at cells CO2 leaves cell, diffuses through interstitial fluid and enters capillary. Driven by pressure gradient. Most of the CO2 enters erythrocytes where the following reaction occurs, catalysed by carbonic anhydrase CO2 + H20 H2CO3 H+ + HCO3- bicarbonate ions leave the RBC and travel to lungs in the plasma. It often combines with Na+ in the plasma to form sodium bicarbonate. In exchange Cl- ions enter RBCs Hydrogen ions bind to haemoglobin ( buffer /Bohr shift) Approx 23% of CO2 binds to amino group of Hb. Binding is influenced by PCO2. High PCO2(i.e. in tissue capillaries) promotes formation of carbaminohaemoglobin.

60. CO2 transport in lungs When the RBCs arrive at the pulmonary capillaries the chemical reaction is reversed. The bicarbonate ions re-enter the cell, combine with the hydrogen ions, forming carbonic acid which then dissociates to carbon dioxide and water. The carbon dioxide diffuses across the capillary wall, enters the alveolus and is exhaled.

62. References Treacher, D.F . and Leach,R.M. (1998) BMJ; 317, p1302-1306 Leach,R.M. and Treacher,D.F. (1998) BMJ, 317, 1370-1373 See Update in Anaesthesia articles on: The physiology of oxygen delivery issue 10 (1999) article 3, p1-3 Oxygen Therapy issue 12 (2000) article 3: p1-3 Oxygen Transport issue 12 (2000) article 11: p1-3 http://www.lakesidepress.com/pulmonary/ABG/PO2.htm