The Physiology of Respiration

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The Physiology of Respiration
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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.

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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 cant make energy - without
  energy cells die

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• 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.

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Figure 01. Oxygen (O2) from the air in the lungs
diffuses into the blood. It is transported in the
blood to the cells. Oxygen diffuses from the
blood into the cells. Carbon dioxide (CO2) from
the cells diffuses into the blood, It is
transported in the blood to the lungs. In the
lungs carbon dioxide diffuses into the air and is
breathed out
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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

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pharynx
epiglottis
larynx
oesophagus
cartilage ring
trachea
rib
intercostal muscles
bronchus
bronchiole
heart
parietal pleura
visceral pleura
left lung
diaphragm
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• 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

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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)

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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

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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)

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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 bodys needs
• Parasympathetic
• Occurs in quiet relaxed situations (rest
  digest)
• Promotes bronchoconstriction
• Sympathetic
• Occurs during exercise / active situations (fight
  or flight)
• Promotes bronchodilation

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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

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Inspiration

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

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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

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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

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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

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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

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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

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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.

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Causes of pulmonary surfactant deficiency
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Work of breathing

• Energy expenditure during breathing depends upon
• Rate and depth of ventilation
• Lung compliance
• Airway resistance

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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?

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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?

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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

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

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• 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.

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Respiratory Control Centres

• Inspiratory centre in medulla oblongata
• Expiratory centre in medulla oblongata
• Apneustic centre in pons
• Pneumotaxic centre in pons

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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).

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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.

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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.

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Pneumotaxic centre
-ve
Apneustic centre
ve
Respiratory centre
-ve
ve
LUNGS
Neuronal control of respiration
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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

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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

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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?

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Gas transport
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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

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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

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Haemoglobin
Each subunit has an iron ion
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Haemoglobin
Oxygen binds to the iron ion
Insufficient iron in the diet means less oxygen
can bind and may result in anaemia
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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

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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

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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

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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

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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

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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

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Hypoxic hypoxia

• Inadequate PO2 in arterial blood (PaO2). May
  results from
• Inadequate PO2 in inspired air
• Major hypoventilation
• Inadequate alveolar capillary transfer

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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

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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.

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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

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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

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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

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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.

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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.

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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