Monthly Archives: August 2013

Ventilation and Perfusion

Definitions

  1. Oxygen delivery (DO2)
    1. The amount of oxygen pumped to the tissues by the heart
  2. Oxygen consumption (VO2)
    1. The amount of oxygen consumed by the tissues
    2. Oxygen demand
      1. The amount of oxygen required by the tissues to function aerobically
      2. May exceed both oxygen delivery and consumption during critical illness
  3. Eupnea – normal breathing pattern
  4. Dyspnea – difficulty breathing, shortness of breath, air hunger
  5. Orthopnea – difficulty breathing unless in a sitting or standing position; not uncommon in severe cardiac and pulmonary disease
  6. Paroxysmal nocturnal dyspnea –  attacks of severe shortness of breath and coughing that generally occur at night
  7. Apnea – cessation of breathing
  8. Tachypnea – >24/min and shallow
  9. Bradypnea – <10/min and regular
  10. Hypoxia – – inadequate cellular O2, partial pressure is around 100 mmHg (13.3 kPa)
  11. Hypercapnia – excess CO2 in the blood, (generally PaCO2 greater than 10 kPa or 75 mmHg
  12. Hypoxemia – deficient arterial PO2, abnormally low level of oxygen in the blood
  13. Hyperventilation – Increased rate and increased depth
  14. Hypoventilation – Decreased rate, decreased depth, and irregular pattern

Measured Parameters

  1. P- partial pressure – In a mixture of gases, each gas has a partial pressure which is the hypothetical pressure of that gas if it alone occupied the volume of the mixture at the same temperature. The partial pressure of a gas is a measure of thermodynamic activity of the gas’s molecules. Gases dissolve, diffuse, and react according to their partial pressures, and not according to their concentrations in gas mixtures or liquids.
  2. Arterial oxygen tension (PaO2) – (Normal range: 80-100 mm Hg) partial pressure of oxygen in arterial blood, typically measured via ABG. It describes the amount of oxygen dissolved in arterial blood plasma.
  3. Arterial carbon dioxide tension (PaCO2) – (Normal range: 35-45 mmHg) partial pressure of arterial carbon dioxide in blood
  4. PVO2 – partial pressure of venous oxygen – (Normal Range: 40 mm Hg)
  5. PVCO2 – partial pressure of venous carbon dioxide – (Normal Range: 46 mm Hg)
  6. P50 – partial pressure of oxygen when the hemoglobin is 50% saturated (Normal Range: 26-28 mmHg).

    Roughly speaking all other things being equal PaO2 and SaO2 relate as follows:
    SaO2 50% = Pa02 26.6 mmHg (aka P50); 70=40; 90=60; 95=80; 99=100 (These numbers change depending on which way the curve shifts.)

  7. Arterial oxygen saturation (SaO2 or SpO2) – (Normal Range: 95-100%) is an estimation of the oxygen saturation level usually measured with a pulse oximeter device. It can be calculated with the pulse oximetry according to the following formula (where HbO2 is the concentration of oxyhemoglobin and Hb is the concentration of deoxyhemoglobin):

    S_\mathrm{p}O_\mathrm{2}=\frac{HbO_\mathrm{2}}{HbO_\mathrm{2}+Hb}

    *Don’t confuse #2 and #7 they are similar, but not the same

  8. Mixed venous oxygen saturation (SvO2) – (Normal Range: 65-70%) Pulmonary artery catheterization allows for obtaining true mixed venous oxygen saturation. Venous O2 saturations differ among several organ systems, since they extract different amounts of O2.
  9. Central venous oxygen saturation (ScvO2)(Normal Range: 25-30%) Central venous catheter reflects principally the degree of oxygen extraction from the brain and the upper part of the body. ScvO2 is usually less than SvO2 by about 2–3% because the lower body extracts less O2 than the upper body making inferior vena caval O2 saturation higher. The primary cause of the lower O2 extraction is that many of the vascular circuits that drain into the inferior vena cava use blood flow for nonoxidative phosphorylation needs (e.g., renal blood flow, portal flow, and hepatic blood flow).
  10. Venous oxygen tension (PvO2) – (Normal Range: 35-45) is the partial pressure of Oxygen in venous blood.
  11. Hemoglobin (Hgb) – (Normal Range: Male: 13.8 to 17.2 gm/d, Female: 12.1 to 15.1 gm/d) is the iron-containing oxygen-transport metalloproteinin the red blood cells. It is a globular protein consisting of four subunits, with each subunit containing a heme moiety, which is an iron-binding porphyrin, and a polypeptid chain, which is designated either alpha or beta. Adult hemoglobin (hemoglobin A) is called alpha 2 beta 2 hemoglobin; two of the subunits have alpha chains and two have beta chains. Each subunit can bind one molecule of O2 per molecule of hemoglobin. When hemoglobin is oxygenated, it is call oxyhemoglobin. For the subunits to bind to O2, iron in the heme moieties must be in the ferrous state (i.e. FE2+). There are several variants of the hemoglobin molecule, the main other varieties include Methemoglobin, Fetal hemoglobin, and Hemoglobin S.
    1. Hemoglobin Synthesis
    2. Oxyhemoglobin Dissociation Curve
      1. Hemoglobin saturation
        1. Rightward shift ==> lower SO2 for given PO2
          1. Hb releases O2 more readily
          2. increased temperature
          3. increased PCO2 (Bohr shift)
            1. The effect of PCO2 & H+ on oxyhemoglobin dissociation curve
          4. increased H+ (decreased pH)
        2. Leftward shift ==> higher SO2 for
          1. given PO2
          2. decreased temperature
          3. decreased PCO2
          4. decreased H+ (increased pH)
          5. decreased 2,3 diphosphoglycerate
          6. (DPG)- associated with stored blood interferes with release of O2 to tissues
      2. Fetal Hemoglobin
        1. The RBCs of a developing fetus contain fetal hemoglobin . The structure of fetal hemoglobin, which differs from that of adult hemoglobin, gives it a much higher affinity for oxygen. Also, fetal hemoglobin binds more oxygen than does adult hemoglobin

    Fetal Hemoglobin

     

    image

    Oxygen Hemoglobin Dissociation Curve Explained
    Oxygen Hemoglobin Dissociation Curve
    Bohr Effect vs. Haldane Effect
  12. Cardiac output (CO) – (Normal Range: 4-8 L/min)
    1. CO= Stroke Volume X Heart Rate
    Physiologic Determinants of Cardiac Output
  13. Alveolar–arterial gradient (A–a gradient)
    1. is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen.
    2. It is used in diagnosing the source of hypoxemia.
    3. Calculated as PAO2 – PaO2
      1. PAO2 is the ‘ideal’ compartment alveolar PO2 determined from the alveolar gas equation
      2. PAO2 = PiO2 – PaCO2/0.8
    4. Increased age affects A-a Gradient (at sea level) (Normal Values)
      1. Age 20 years: 4 to 17 mmHg
      2. Age 40 years: 10 to 24 mmHg
      3. Age 60 years: 17 to 31 mmHg
      4. Age 80 years: 25 to 38 mmHg
    5. Interpretation: Hypoxemia causes differentiated by A-a Gradient
      1. Increased A-a Gradient
        1. V/Q Mismatch
          1. Congestive Heart Failure
          2. Adult Respiratory Distress Syndrome (ARDS)
          3. Pneumonia
          4. Atelectasis
        2. Pulmonary shunt
          1. Pulmonary Embolism
          2. Patent Foramen Ovale
          3. Atrial Septal Defect
        3. Alveolar hypoventilation
          1. Interstitial Lung Disease
      2. Normal A-a Gradient
        1. Hypoventilation
          1. Neuromuscular disorders
          2. Central nervous system disorder
        2. Low inspired FIO2 (e.g. high altitude)

Respiratory Volumes and Rates

File:Flow-volume-loop.svg

  1. Total Lung Capacity (TLC) – 6.0 L (averages around 6000 ml in males and 4500 ml in females)
    1. is the total volume of your lungs. The sum of the vital capacity and the residual volume
  2. Functional Residual Capacity (FRC) – 2.4 L
    1. is the amount of air remaining in your lungs after you have completed a quiet respiratory cycle. The FRC is the sum of the expiratory reserve volume and the residual volume.
  3. Vital Capacity (VC) – 4.7 L
  4. (Resting) Tidal Volume (VT) – 0.5 L
    1. is the amount of air you move into or out of your lungs during a single respiratory cycle under resting conditions.
  5. Expiratory Reserve Volume – 1000 ml
    1. is the amount of air that you can voluntarily expel after you have completed a normal, quiet respiratory cycle. As an example, if, with maximum use of the accessory muscles, you can expel an additional 1000 ml of air, your expiratory reserve volume is 1000 ml.
  6. Residual Volume – about 1200 ml in males and 1100 ml in females
    1. is the amount of air that remains in your lungs even after a maximal exhalation
  7. Minimal Volume – ranges from 30 to 120 ml
  8. Inspiratory Reserve Volume – males averages 3300 ml, compared with 1900 ml in females
    1. is the amount of air that you can take in over and above the tidal volume. Inspiratory reserve volumes differ significantly by gender, because, on average, the lungs of males are larger than those of females.
  9. Breathing Rate – 15-20 breaths/min
  10. Physiologic Dead Space (VD) – Normal Values ~0.15 L
    1. VD = VT x ((Paco2 – PEco2)/Paco2)
      1. VD = Physiologic Dead Space (mL)
      2. VT = Tidal Volume (mL)
      3. Paco2 = PCO2 of arterial blood (mm Hg)
      4. PEco2 = PCO2 of mixed expired air (mm Hg)
    2. The concept of physiologic dead space is more abstract than the concept of anatomic dead space. By definition, the physiologic dead space is the total volume of the lungs that does not participate in gas exchange. Physiologic dead space includes the anatomic dead space of the conducting airways plus a functional dead space in the alveoli.
    3. The functional dead space can be thought of as alveoli that do not participate in gas exchange. The most important reason that alveoli do not participate in gas exchange is a mismatch of ventilation and perfusion, or so-called ventilation/perfusion defect, in which ventilated alveoli are not perfused by pulmonary capillary blood.
    4. In normal persons, the physiologic dead space is nearly equal to the anatomic dead space. The ratio of physiologic dead space to tidal volume provides an estimate of how much ventilation is “wasted” (either in the conducting airways or in nonperfused alveoli).
      1. Anatomic Dead Space can increase via:
        1. Body size
        2. Lung Volume
        3. Posture
          1. supine posture supine ~ 101 ml
          2. sitting ~ 147 ml (Fowler)
        4. Respiratory flow pattern
          1. decreased, using Fowler technique, with low VT due to the mixing effect of the heart beat below the carina, and the cone advance of laminar flow, seen at low flow velocities
        5. Lung Disease – emphysema
        6. Loss or excision of lung
        7. Endotracheal Intubation, but there is the additional volume of the circuit
        8. Position of the Jaw & Neck – increases with jaw protrusion in non-intubated
    5. 562 FA 12 : PHYSIOLOGIC DEAD SPACE AND MEASURING
  11. Forced Vital Capacity (FVC) – 4.7 L
    1. This is the total volume of air expired after a full inspiration. Patients with obstructive lung disease usually have a normal or only slightly decreased vital capacity. Patients with restrictive lung disease have a decreased vital capacity
  12. Forced Expiratory Volume in 1 Second (FEV1) – 80-120% is normal
    1. This is the volume of air expired in the first second during maximal expiratory effort. The FEV1 is reduced in both obstructive and restrictive lung disease. The FEV1 is reduced in obstructive lung disease because of increased airway resistance. It is reduced in restrictive lung disease because of the low vital capacity.
  13. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) – (Normal Value: 75-125%)
    1. The DLCO is designed to reflect properties of the alveolar-capillary membrane, specifically the ease with which oxygen moves from inhaled air to the red blood cells in the pulmonary capillaries. The uptake of most soluble gases (such as nitrous oxide or acetylene) is limited by (and varies with) pulmonary blood flow. In contrast, the strong affinity of hemoglobin for carbon monoxide (CO), combined with the enormous capacity of the red cell mass to absorb CO, make the uptake of CO less dependent on cardiac output. Thus, diseases in which the uptake of oxygen is reduced cause parallel decreases in the uptake of CO, as measured by the DLCO.
    2. Carbon monoxide can be used to measure the diffusing capacity of the lung. The diffusing capacity of the lung is decreased in parenchymal lung disease and COPD (especially emphysema) but is normal in asthma.

Constants

  1. Atmospheric (barometric) pressure (PATM or PB) – 760 mm Hg (at sea level)
  2. Water vapor pressure (PH2O) – 47 mm Hg (37C)
  3. Standard temperature, pressure, dry (STPD) – 273 K, 760 mm Hg
  4. Body temperature, pressure, saturated (BTPS) – 310 K, 760 mm Hg, 47 mm Hg
  5. Solubility of O2 in blood – 0.003 ml O2/100 ml blood/mm Hg
  6. Solubility of CO2 in blood – 0.07 ml CO2/100 ml blood/mm Hg

Calculated Parameters

  1. Cardiac index (CI) – (Normal Range: 2.6 – 4.2 L/min per square meter) 

    The index is usually calculated using the following formula: CI = \frac{CO}{BSA} = \frac{SV*HR}{BSA}

        1. CI=Cardiac index
        2. BSA=Body surface area
        3. SV=Stroke volume
        4. HR=Heart rate
        5. CO=Cardiac output

    image

  2. Alveolar Oxygen Tension
    1. PAO2 = FiO2 x [(PB-PH20)–(PaCO2/RQ)]
    2. PB= barometric pressure,
    3. PH2O = water vapor pressure
    4. RQ = respiratory quotient
    5. For example, PAO2= 0.30 x [(760 torr – 47 torr) – (40 torr / 0.8)]
      1. assuming normal values described below
      2. 0.30 = FiO2
      3. 760 = barometric pressure
      4. 47 = water vapor pressure
      5. 40 = PaCO2
      6. 0.8 = Respiratory Coefficient
    6. PAO2= 0.30 x 663 torr = 199 torr
    7. PAO2 can also be approximated rapidly at the bedside as 700 as torr x FiO2- 50 torr
    8. PAO2 can also be approximated with the formula (patient age in years/4)+4 if the actual is much greater than this it can indicate a possible pulmonary embolism
    9. The torr is a traditional unit of pressure, now defined as exactly 1/760 of a standard atmosphere, which in turn is defined as exactly 133.322368 pascals. Historically, one torr was intended to be the same as one “millimeter of mercury”.
  3. Pulmonary end-capillary oxygen content (CcO2) in vol% –
    1. (1.34 * Hgb * 1) + (PAO2 * 0.0031)

      Oxygen Bound + Oxygen Dissolved

      (Normal value depends on the Hgb level and the FiO2)

      1. Hgb = hemoglobin content in g%
      2. 1.34 = Amount of oxygen that 1 g of fully saturated hemoglobin can hold
      3. PAO2 = Alveolar oxygen tension in mm Hg, used in place of end-capillary PO2 (PCO2)
      4. 0.0031 = Amount of dissolved oxygen for 1 mm Hg of PaO2
    2. Note again that alveolar (PAO2) and not arterial (PaO2) oxygen tension is used in this equation
    3. The oxygen content of pulmonary end-capillary blood as it leaves the alveolus.
    4. Represents the best oxygen content possible at the end-capillary level and reflects the optimal oxygen carrying capacity of the cardiopulmonary system. The oxygen saturation is assumed to be 100%. The major determinant of CCO2 is the hemoglobin level. Therefore, a low hemoglobin level like in anemia significantly lowers the end-capillary oxygen content.
    5. It is also used in other calculations like the shunt equation.
  4. Arterial oxygen content (CaO2) (Normal Range: 17-20ml/dl)
    1. CaO2 = 1.34 X Hgb X SaO2
    2. CaO2 = O2 dissolved in Plasma + O2 combined with Hgb
    3. Calculated by adding the volume of oxygen dissolved in the plasma and the volume of combined oxygen
    4. YouTube Example – Calculating Total Oxygen Content / CaO2 (not the one shown below)
    Content of Arterial Oxygen Calculation
  5. Venous oxygen content (CvO2)  – Normal Range 12-15 vol%
    1. CvO2 = (Hgb x 1.34 x SvO2) + (PvO2 x 0.0031)
      1. Hgb = hemoglobin content in g%
      2. 1.34 = Amount of oxygen that 1 g of fully saturated hemoglobin can hold
      3. SvO2 = mixed venous oxygen saturation in Vol%
      4. PvO2 = mixed venous oxygen tension mm Hg, measured via blood gas, or estimated as 35 torr
        1. (1.34 x 15 g x 0.75) + (35 torr x 0.0031) (assuming normal mixed venous oxygen saturations) = 15.1 ml O2/dl blood + 0.11 ml O2/dl blood = 15.2 ml O2/dl blood
      5. 0.0031 = Amount of dissolved oxygen for 1 mm Hg of PaO2
    2. Mixed venous oxygen content reflects the overall oxygen level of the blood returning to the right heart, and is affected by a number of factors. Low hemoglobin levels (e.g. anemia), low oxygen saturation (e.g. hypoxemia), decrease in cardiac output (e.g. congestive heart failure), or an increase in metabolic rate (e.g. exercise) significantly lower the CvO2
  6. Arterial-venous oxygen content difference (Ca-vO2) (Normal Range: 4.2-5.0ml/dl)
    1. Ca-vO2 = CaO2 – CvO2
      1. Ca or CaO2 = Oxygen content of the arterial blood (mL O2/ 10 mL blood) in Vol% 
      2. CvO2 = mixed venous oxygen content in Vol%
    2. Myocardial Oxygen Extraction
    3. The difference in oxygen content between arterial and venous blood
      1. Represents the amount of oxygen used during one pass of blood through the body
      2. Can be used as an estimate of the patient the patient’s physiologic oxygen reserve
      3. Useful in assessing changes in oxygen consumption and cardiac output
      4. Under conditions of normal oxygen consumption and cardiac output, about 25% of the available oxygen is used for tissue metabolism. Therefore, a Ca-vO2 of 5 vol% (CaO2 20% vol%  – CvO2 15 vol%) reflects a balanced relationship between oxygen consumption and cardiac output.
      5. If the cardiac output stays unchanged or is unable to compensate for hypoxia, an increase of oxygen consumption (metabolic rate) will cause an increase Ca-vO2. A decrease oxygen consumption will cause a decrease in Ca-vO2.
      6. Central Venous and Mixed Venous Oxygen Saturation in Critically Ill Patients

        image

      7. Factors that decrease Ca-vO2
        1. Increased cardiac output
        2. Skeletal muscle relaxation (e.g. induced by drugs)
        3. Peripheral Shunting (e.g. sepsis, trauma)
        4. Certain Poisons (e.g. cyanide prevents cellular metabolism)
        5. Hypothermia
  7. Oxygen Utilization Coefficient = Oxygen Extraction Ratio or O2ER (Normal Range: 24-28%)
    1. Oxygen utilization coefficient (OUC) = VO2I / DO2I = ~0.25
      1. If the SaO2 is maintained at a relatively high level (> 0.92), the OUC can be approximated as: = 1- SvO2
    2. Shown again, the OUC or oxygen extraction ratio (O2ER) is the ratio of Formula to Formula and represents the fraction of oxygen delivered to the microcirculation that is taken up by the tissues.

    Formula

    The normal O2ER is 0.2 to 0.3, indicating that only 20–30% of the delivered oxygen is utilized. This spare capacity enables the body to cope with a fall in Formula without initially compromising aerobic respiration and Formulavaries between organs; the heart has a high O2ER (∼0.6) so it is particularly sensitive to reductions in coronary artery Formula.

  8. Oxygen delivery index (DO2I) (Normal Range: 550-650ml/min/m2)
    1. Volume of gaseous oxygen pumped from the left ventricle per minute per meter squared BSA
    2. DO2I = CI x CaO2 x 10 x dL/L
      1. The 10 dL/L corrects for the fact that CI is measured in L/min/m2 and oxygen content is measured in ml/dl
      2. This is a very important resuscitation endpoint for ensuring adequate oxygen delivery to the tissues
    Delivery of Oxygen to the Tissues–Explained without the indexes used here
  9. Oxygen consumption index (VO2I) (Normal Range: 115-165ml/min/M2)
    1. Volume of gaseous O2 returned to the right atrium per minute per meter squared BSA
    2. VO2I = CI x Ca-v O2 x 10 x dL/L
      1. The 10 dL/L corrects for the fact that CI (Cardiac Index) is measured in L/min/m2 and oxygen content is measured in ml/dl
    3. VO2I = oxygen consumption index = volume of gaseous O2 consumed by the body per minute per meter squared BSA = volume of oxygen leaving the heart – volume of oxygen returning to the heart = [(CI x CaO2) – (CI x CvO2)] x 10dL/L = CI x Ca-vO2 x 10 dL/L = ~150 ml O2/min.m2
    4. It is the amount of oxygen consumed by the tissue per minute indexed to BSA
  10. Intrapulmonary shunt (Qsp/Qt) or venous admixture (Normal Range: 3-5) 

    Venous Admixtureimage

  11. Intrapulmonary Shunt
    1. A V/Q ratio below 1.0 describes the condition where capillary blood flow is excessive relative to ventilation. The excess blood flow, know as intrapulmonary shunt, does not participate in pulmonary gas exchange. There are two types of intrapulmonary shunt.
      1. True shunt indicates the total absence of exchange between capillary blood and alveolar gas (V/Q = 0), and is equivalent to an anatomic shunt between the right and left sides of the heart.
      2. Venous admixture represents the capillary flow that does not equilibrate completely with alveolar gas (0 < V/Q < 1). As the venous admixture increases, the V/Q ratio decreases until it reaches true shunt conditions (V/Q = 0).
    2. The fraction of the cardiac output that represents intrapulmonary shunt is known as the shunt fraction.
      1. In normal subjects, intrapulmonary shunt flow (Qs) represents less than 10% of total cardiac output (Qt), so the shunt fraction (Qs/Qt) is less than 10%.
      2. Intrapulmonary shunt fraction increases when small airways are occluded (e.g. asthma), when alveoli are filled with fluid (e.g. pulmonary edema, pneumonia), when alveoli collapse (e.g. atelectasis), or when capillary flow is excessive (e.g. nonembolized regions of lung in pulmonary embolism).
    3. For individuals who are breathing spontaneously
      1. Qsp/Qt = (CcO2 – CaO2) / (5 + CcO2 – CaO2)
    4. For critically ill patients receiving mechanical ventilation with or without PEEP
      1. Qsp/Qt = (CcO2 – CaO2) / (3.5 + CcO2 – CaO2)
        1. CcO2 = end capillary oxygen content vol%
        2. CaO2 = arterial oxygen content vol%
        3. Constants are either 5 or 3.5 cm H2O
    5. Blood which does not pass through ventilated portions of the lung and leaves the lung desaturated
      1. Normal  intrapulmonary shunt sun is 2-5%
      2. May exceed 50% in patients with severe acute respiratory distress syndrome (ARDS)
    6. The estimated shunt equation does not require a mixed venous blood sample. It is less accurate than the physiologic shunt equation. In normal subjects 5 vol% may be used as the estimated arterial mixed venous oxygen content difference Ca-vO2 as a result of the increased cardiac output or decreased oxygen consumption (extraction).
    7. Degree of Intrapulmonary Shunt
      1. A calculated shunt of less than 10% is normal in clinical settings.
      2. A shunt of 10-20% indicates mild intrapulmonary shunting, and
      3. a shunt of 20-30% indicates a significant intrapulmonary shunting.
      4. Greater than 30% of the calculated shunt reflects critical and severe intrapulmonary shunting.

      image

    8. With a 50 % shunt of QT , increase in FIO2 results in no increase in PAO2, therefore, in this case treatment of hypoxemia is not increasing the FIO2 , and is decreasing the percentage of the shunt ( bronchoscopy , peep , positioning , antibiotics , suctioning , diuretics )
      1. PAO2 is directly related to FIO2 in normal patients
    9. Qsp/Qt is increased in one or more of the following categories of shunt producing disease:
      1. Anatomic shunt (congenital heart disease, intrapulmonary fistulas, vascular lung tumors)
      2. Capillary shunt (atelectasis, alveolar fluid)
      3. venous admixture (hypoventilation, uneven distribution of ventilation, diffusion defects)
    10. Abnormal Intrapulmonary shunt
      1. There are a number of sources of Qsps/Qt in the critically ill
        1. Atelectasis
        2. Lobar pneumonia
        3. Inhalation injury
        4. Drowning
        5. Acute Respiratory Distress Syndrome (ARDS)
        6. Abdominal Compartment Syndrome (ACS)
      2. Represents an “oxygen refractory” hypoxemia
        1. Shunted blood is not exposed to ventilated alveoli
        2. Can not be improved with supplemental oxygen regardless of the oxygen fraction administered
      3. Knowing how Qsps/Qt is calculated is important
        1. Definitions
          1. Qt = total cardiac output in L/min
          2. Qs = shunted portion of cardiac output
          3. Qns = normal pulmonary end-capillary blood flow that is not shunted past abnormal alveoli
          4. Therefore, Qt = Qs + Qns
          5. Total blood flow = shunted + non-shunted blood
        2. Further definitions
          1. Qt * CaO2 = total oxygen delivered to the body
            *The equation for oxygen delivery (DO2)
          2. Qs * CvO2 = total oxygen within shunted blood
            *No oxygen is added; content remains CvO2
          3. Qns * CcO = total oxygen within end-capillary blood capillary blood
          4. Therefore,
            Qt (CaO2) = Qs (CvO2) + Qns (CcOc2)
            *Total oxygen delivered = sum of the oxygen within shunted and non-shunted blood
          5. Qt (CaO2) = Qs (CvO2) + (Qt – Qs)(CcO2)
            1. Substituting (Qt – Qs) for Qns…
          6. Qt (CaO2) = Qs (CvO2) + Qt (CcO2) – Qs (CcO2)
            1. Rearranging…
          7. Qs (CcO2 – CvO2) = Qt (CcO2 – CaO2)
            1. Further rearranging…
          8. Qs/Qt = (CcO2 – CaO2) / (CcO2—CvO2)
            1. The Shunt Equation
        3. Shunt Calculation Example

Darcy’s Equation

  1. Flow = Blood Pressure / Peripheral Vascular Resistance
  2. When applied to the circulatory system, we get
    1. Q = (MAP – RAP)/TPR
      1. Q = Cardiac Output
      2. Where MAP = Mean Aortic (or Arterial) Blood Pressure in mmHg
      3. RAP = Mean Right Atrial Pressure in mmHg and
      4. TPR = Total Peripheral Resistance in dynes-sec-cm-5.
    2. However, as MAP>>RAP, and RAP is approximately 0, this can be simplified to
    3. Q ≈ MAP/TPR
    4. For the right heart Q ≈ MAP/PVR, while for the left heart Q ≈ MAP/SVR.
      1. MAP = Mean Arterial Pressure
      2. PVR = Pulmonary Vascular Resistance
      3. SVR = Systemic Vascular Resistance
  3. Physiologists will often re-arrange this equation, making MAP the subject, to study the body’s responses.As has already been stated, Q is also the product of the heart rate (HR) and the stroke volume (SV), which allows us to say:
  4. Q ≈ (HR × SV) ≈ MAP / TPR
  5. It is a generalized relationship for flow in porous media. It shows the volumetric flow rate is a function of the flow area, elevation, fluid pressure and a proportionality constant. It may be stated in several different forms depending on the flow conditions. Since its discovery, it has been found valid for any Newtonian fluid.
  6. Darcy’s Law Basics and More
Darcy’s Equation for Linear Flow

    Darcy’s Law – Example

    Oxygen Calculations

    1. Knowledge of the oxygen transport equations is essential to understanding the pathophysiology and appropriate treatment for the various shock states
    2. Pulmonary artery and central venous oximetry catheters provide the ability to monitor oxygen transport balance at the bedside
      1. Continuous mixed venous oximetry (SvO2)
      2. Continuous central venous oximetry (ScvO2)
      3. SvO2 Vs ScvO2
      4. SvO2 Vs ScvO2
      5. The SvO2 and ScvO2 change in parallel when the whole body ratio of O2 supply to demand is altered. For instance, the difference between the absolute value of ScvO2 and SvO2 changes under conditions of shock. In septic shock ScvO2 often exceeds SvO2 by about 8%. During cardiogenic or hypovolemic shock mesenteric and renal blood flow decreases followed by an increase in O2 extraction in these organs. In septic shock regional O2 consumption of the gastrointestinal tract and hence regional O2 extraction increases despite elevated regional blood flows. On the other hand, cerebral blood flow is maintained over some period in shock. This would cause a delayed drop of ScvO2 in comparison to SvO2, and the correlation between these two parameters would worsen. Some authors therefore argued that ScvO2 cannot be used as surrogate for SvO2 under conditions of circulatory shock.

        However, changes in SvO2 are closely mirrored by changes in ScvO2 under experimental and clinical conditions despite a variable difference between these two variables.

        This may explain why Rivers et al. were able to use ScvO2 higher than 70% in addition to conventional hemodynamic parameters as therapeutic endpoint for hemodynamic resuscitation to improve outcome in patients with severe sepsis and septic shock.

        From a physiological point of view, SvO2 monitoring for “early goal directed therapy” should provide similar results. Given the fact that ScvO2 exceeds SvO2 on average by 8% in patients with septic shock, a SvO2 of about 62–65% should suffice as endpoint for hemodynamic resuscitation in these conditions, although this has not been tested prospectively. However, the placement of pulmonary artery catheters and the potentially higher risk of this should not result in a delay in the start of the resuscitation of critically ill patients.

        Venous oximetry can reflect the adequacy of tissue oxygenation only if the tissue is still capable of extracting O2. In the case of arteriovenous shunting on the microcirculatory level or cell death, SvO2 and ScvO2 may not decrease or even show elevated values despite severe tissue hypoxia.

      6. Intermittent calculation of oxygen delivery
        1. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I)
        2. Once the oxygen contents throughout the vascular circuit have been calculated, the amount of oxygen delivered to the tissues (oxygen delivery index or DO2I) and the amount of oxygen consumed by the tissues (oxygen consumption index or VO2I) can be calculated.
        3. DO2I = oxygen delivery index = volume of gaseous O2 pumped from the left ventricle per minute per meter squared BSA = CI x CaO2 x 10 dL/L (the 10 dL/L corrects for the fact that CI is measured in L/min/m2 and oxygen content is measured in ml/dl) = ~600 ml O2/min.m2
        4. VO2I = oxygen consumption index = volume of gaseous O2 consumed by the body per minute per meter squared BSA = volume of oxygen leaving the heart – volume of oxygen returning to the heart = [(CI x CaO2) – (CI x CvO2)] x 10dL/L = CI x Ca-vO2 x 10 dL/L = ~150 ml O2/min.m2
        5. Two oxygenation parameters characterize the relative balance between oxygen delivery and oxygen consumption (“supply versus demand”):
          1. the oxygen utilization coefficient (OUC) and
          2. the mixed venous oxygen saturation (SvO2).
        6. The OUC, also known as the oxygen extraction ratio or O2ER, is the percentage of delivered oxygen which is consumed by the body and is calculated as follows:
          1. OUC = Oxygen utilization coefficient = VO2I / DO2I = ~0.25
          2. If the SaO2 is maintained at a relatively high level (> 0.92), the OUC can be approximated as: = 1- SvO2
        7. If the SaO2 is maintained at a relatively high level (> 0.92), the OUC can be approximated as: = 1- SvO2

    3. Fraction of Inspired Oxygen
      1. Fraction of inspired oxygen (FiO2) is the fraction or percentage of oxygen in the space being measured. Medical patients experiencing difficulty breathing are provided with oxygen-enriched air, which means a higher-than-atmospheric FiO2. Natural air includes 20.9% oxygen, which is equivalent to FiO2 of 0.21. Oxygen-enriched air has a higher FiO2 than 0.21, up to 1.00, which means 100% oxygen. FiO2 is typically maintained below 0.5 even with mechanical ventilation, to avoid oxygen toxicity.
      2. Example:
        with a nasal cannula, we assume that the fraction of oxygen that is inspired (above the normal atmospheric level or 20%) increases by 4% for every additional liter of oxygen flow administered.
      Oxygen tank FLOW RATE in liters / min FiO2 — Fraction of Inspired Oxygen value
      0 (no oxygen, just room air) .20
      1 L / min .24
      2 L / min .28
      3 L / min .32
      4 L / min .36
      5 L / min .40
      6 L / min .44
    4. Oxygen bound = Hgb conc x oxygen Hgb can carry x Hgb saturation
      1. The O2-binding capacity is the maximum amount of O2 that can be bound to hemoglobin per volume of blood, assuming that hemoglobin is 100% saturated (i.e., all four heme groups on each molecule of hemoglobin are bound to O2). The O2-binding capacity is measured by exposing blood to air with a very high PO2 (so that hemoglobin will be 100% saturated) and by correcting for the small amount of O2 that is present in the dissolved form. (To correct for dissolved O2, remember that the solubility of O2 in blood is 0.003 ml O2/100 ml blood/mm Hg.) Other information needed to calculate the O2-binding capacity is that 1 g of hemoglobin A can bind 1.34  ml O2 and that the normal concentration of hemoglobin A in the blood is 15 g/100 ml. The O2-binding capacity of blood is therefore
        1. 20.1 ml O2/100 ml blood = 15 g/100 ml x  1.34 ml O2/g hemoglobin = 20.1 ml O2/100 ml blood
      2. The figure below illustrates the MWC model for a hypothetical tetrameric protein that binds a ligand A. There are only two states the subunits can adopt, T (low affinity for A – squares) and R (high affinity, circles). In addition, no subunit can be t state unless all subunits are in the T state, and the same for the R state. Thus, there are only 2 fully symmetric quaternary states of the protein, T and R. Each protein molecule, whether T or R, can bind 0, 1, 2, 3, or 4 ligands, giving rise to all the equilibriums shown.

      image

    Gas Laws

    1. Atmospheric Gas
      1. Barometric pressure is the sum of all gases exerting pressure on the earths surface. At sea level Atmospheric pressure is 760 mmHg. The primary components of this pressure is nitrogen, oxygen, argon and carbon dioxide.
    2. Ideal Gas Law
      1. The ideal gas law is the equation of state of a hypothetical ideal gas. It is a good approximation to the behavior of many gases under many conditions, although it has several limitations.
      2. PV = nRT
        1. P = pressure
        2. V = volume
        3. n = # of moles
        4. R = 8.31441 J K-1 mol-1
        5. T = Temperature
      3. Khan Academy – Ideal Gas Law

    3. Fick’s Law
      1. The diffusion of gas takes place according to Fick’s law it states that the rate of gas transfer across a sheet of tissue is directly proportional to
        1. the surface area of the tissue,
        2. to the diffusion constant
        3. the difference in partial pressure of the gas between the two sides of the tissue
        4. inversely proportional to the thickness of the tissue.
      2. Khan Academy – Fick’s Law of Diffusion
    4. Henry’s Law
      1. Henry’s law states that at a constant temperature, the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid.
      2. The amount of gas that can be dissolved by 1 ml of a given liquid at standard pressure and specified temperature is known as the solubility coefficient.
        1. Water Solubility of CO2 = 0.592
        2. Water Solubility of O2 = 0.0244
      3. The solubility of CO2 is about 24 times greater than O2.
      4. Khan Academy – Henry’s Law
    5. Graham’s Law
      1. Graham’s law states states the rate of diffusion or effusion for a gas is inversely proportional to the square root of the molar mass of the gas of a gas
      2. The diffusion rate of CO2 is 20 times greater than that of O2
      3. Khan Academy – Graham’s Law of of Effusion
      4. BrightStorm – Graham’s Law
    6. Boyle’s Law
      1. Boyle’s Law states that the product of the pressure and volume for a gas is a constant for a fixed amount of gas at a fixed temperature
      2. BrightStorm – Boyle’s Law
    7. Charles’s Law
      1. The volume of a given mass of an ideal gas is directly proportional to its temperature on the absolute temperature scale (in Kelvin) if pressure and the amount of gas remain constant; that is, the volume of the gas increases or decreases by the same factor as its temperature
      2. V/T = k
        1. V = the volume of the gas
        2. T = the temperature of the gas (measured in Kelvin)
        3. K = is a constant
      3. This law explains how a gas expands as the temperature increases; conversely, a decrease in temperature will lead to a decrease in volume. For comparing the same substance under two different sets of conditions, the law can be written as:

      \frac{V_1}{T_1} = \frac{V_2}{T_2} \qquad \mathrm{or} \qquad \frac {V_2}{V_1} = \frac{T_2}{T_1} \qquad \mathrm{or} \qquad V_1 T_2 = V_2 T_1.

    8. Avogadro’s Law
      1. The principle that equal volumes of all gases under identical conditions of pressure and temperature contain the same number of molecules
      2. Stated another way that under equal conditions of temperature and pressure, equal volumes of gases contain an equal number of molecules.
      3. V/n = k
        1. V = volume of the gas
        2. n = is the amount of the substance of the gas
        3. k = is a proportionality constant
      4. One mole of an ideal gas occupies 22.4 liters (dm³) at STP, and occupies 24.45 liters at SATP (Standard Ambient Temperature and Pressure = 273K and 1 atm or 101.325 kPa). This volume is often referred to as the molar volume of an ideal gas. Real gases may deviate from this value.
      5. STP corresponds with 1 atm pressure (760 torr) and 0 oC.

    4 Primary Questions

      1. PCO2 equation
        1. PACO2 = VCO2 x 0.863 / VA
          1. where VA=VE-VD
            1. VE = minute ventilation
            2. VD = dead space per minute
          2. 0.863 = is necessary to equate dissimilar units for VCO2 (ml/min) and VA (L/min) to PACO2pressure units (mm Hg)
          3. VA = alveolar ventilation
        2. The PCO2 equation puts into physiologic perspective one of the most common of all clinical observations: a patient’s respiratory rate and breathing effort. The equation states that alveolar PCO2 (PACO2) is directly proportional to the amount of CO2 produced by metabolism and delivered to the lungs (VCO2) and inversely proportional to the alveolar ventilation (VA). While the derivation of the equation is for alveolar PCO2, its great clinical utility stems from the fact that alveolar and arterial PCO2 can be assumed to be equal.
        3. We primarily need to know if VA is adequate for VCO2; if it is, then PaCO2 will be in the normal range (35-45 mm Hg). Conversely, a normal PaCO2 means only that alveolar ventilation is adequate for the patient’s level of CO2 production at the moment PaCO2 was measured.  From the PCO2 equation it is evident that a level of alveolar ventilation inadequate for CO2 production will result in an elevated PaCO2 (> 45 mm Hg; hypercapnia). Thus patients with hypercapnia are hypoventilating (the term hypoalveolar ventilating would be more appropriate but hypoventilating is the conventional term). Conversely, alveolar ventilation in excess of that needed for CO2 production will result in a low PaCO2 (< 35 mm Hg; hypocapnia) and the patient will be hyperventilating. (Confusion sometimes arises because the prefix (hyper-, hypo-) differs for the same condition depending on whether one is describing a blood value or the state of alveolar ventilation.)
        4. From the PCO2 equation it follows that the only physiologic reason for elevated PaCO2 is a level of alveolar ventilation inadequate for the amount of CO2 produced and delivered to the lungs. Thus arterial hypercapnia can always be explained by:
            1. not enough total ventilation (as may occur from central nervous system depression or respiratory muscle weakness); or
            2. too much of the total ventilation ending up as dead space ventilation (as may occur in severe chronic obstructive pulmonary disease, or from rapid, shallow breathing); or
            3. some combination of 1) and 2)
        5. An important clinical corollary of the PaCO2 equation is that we cannot reliably assess the adequacy of alveolar ventilation – and hence PaCO2 – at the bedside. Although VE can be easily measured with a handheld spirometer (as tidal volume times respiratory rate), there is no way to know the amount of VE going to dead space or the patient’s rate of CO2 production. A common mistake is to assume that because a patient is breathing fast, hard and/or deep he or she must be “hyperventilating.” Not so, of course.
        What determines pCO2
      2. Henderson-Hasselbalch equation
        1. pH = pK + log HCO3 / 0.03(PaCO2)
          1. pH ~ HCO3 / PaCO2
          2. .03  mmol/L/mm Hg solubility of CO2
          3. pKa = acid dissociation constant
        2. It is used to calculate the PH of a buffered solution. This equation is derived from the behavior of weak acids (and bases) in solution, which is described by the kinetics of reversible reactions.
        3. EMCrit Podcast 44 – Acid Base: Part I
        Buffers and Hendersen-Hasselbalch
        How Do Buffers Work? (Henderson-Hasselbalch Example)
        Henderson-Hasselbach Equation

      3. Alveolar Gas equation, and
        1. PAO2 = FIO2(PATM-PH2o)-PACO2[FIO2 + (1-FIO2) / R]
          1. Abbreviated form
            1. PAO2=FIO2(PATM-47)-1.2(PaCO2)
              1. R = 0.8 (assuming identical values for arterial and alveolar PCO2)
              2. 47 = Water vapor pressure in the airways is dependent only on body temperature and is 47 mm Hg at normal body temperature (37 degrees C)
              3. PATM = is usually not necessary to measure PATM if you know its approximate average value where the blood was drawn (e.g. sea level 760 mm Hg; Cleveland 747 mm Hg; Denver 640 mm Hg)
              4. 1.2 = is a factor based on assumed respiratory quotient (CO2 excretion over O2 uptake in the lungs) of 0.8; this factor becomes 1.0 when the FIO2is 1.0.
        2. All physicians know that hemoglobin carries oxygen and that anemia can lead to severe hypoxemia. Making the necessary connection between PaO2 and O2 content requires knowledge of the oxygen content equation.
        3. The alveolar gas equation predicts the change in PAO2 that will occur for a given change in PACO2. Because the normal value for the respiratory exchange ratio is 0.8, when alveolar ventilation is halved, the decrease in PAO2 will be slightly greater than the increase in PACO2. To summarize, when VA is halved, PACO2 is doubled and PAO2 is slightly more than halved.
        Alveolar Gas Equation – Part 1
        Alveolar Gas Equation – Part 2
        Oxygen Movement from Alveoli to Capillaries
      4. Oxygen Content equation
        1. CaO2 = (SaO2 x Hb x 1.34) + .003(PaO2)
          1. where:
            1. SaO2 = is an estimation of the oxygen saturation level usually measured with a pulse oximeter device
            2. 1.34 = ml O2/gram Hb = Amount of oxygen that 1 g of fully saturated hemoglobin can hold
            3. .003 = ml   O2/mm Hg  PaO2/dl =  represents the amount of oxygen dissolved in plasma
            4. Hb = hemoglobin content in grams/dl
            5. PaO2 = is a measurement of pressure exerted by uncombined oxygen molecules dissolved in plasma
          2. The oxygen content is the actual amount of O2 per volume of blood. The O2 content can be calculated from the O2-binding capacity of hemoglobin and the percent saturation of hemoglobin, plus any dissolved O2.
          3. Examples Oxygen Content Calculator
    Oxygen Content

    Vascular Circuit

    1. Central to any assessment of oxygen transport is the ability to calculate the
      amount of oxygen in the blood at any point in the body

    Such calculations are dependent upon both the measured oxygen tension
    and oxygen saturation at each point

    image

    gas_exchangeimage

    image

    Hypoxia Shunts and Ventilation Perfusion Mismatch

    image 

    Control of Breathing

    1. Rhythmicity of respiration is primarily controlled by specific neural areas in the medulla and pons of the brain.
    2. These areas possess monitoring, stimulating and inhibiting properties that continually adjust ventilatory pattern to meet specific metabolic needs
    3. To understand how control of ventilation occurs, one must have a basic knowledge of:
      1. the function of respiratory components of the medulla
      2. the influence of the pontine respiratory centers on the respiratory components of the medulla
      3. the monitoring systems that influence respiratory components of the medulla
      4. the reflexes that influence ventilation

    The Respiratory Components of the Medulla

    1. Two groups of respiratory neurons in the medulla oblongata are responsible for coordinating the intrinsic rhythmicity of respiration:
      1. dorsal respiratory group (DRG)
      2. ventral respiratory group (VRG)
      The Respiratory Center

      Dorsal Respiratory Group

      1. The dorsal respiratory group (DRG) consists chiefly of inspiratory neurons.
      2. Believed to be responsible for the basic rhythm of ventilation.
      3. The DRG:
        1. receive signals regarding respiratory needs
        2. evaluate and prioritize various signals
        3. emit neural impulses every few seconds to the muscles of inspiration
      4. cells within the DRG are thought (West) to posses inherent rhythmicity, generating bursts of neuronal activity to the diaphragm and respiratory muscles in the absence of any other input
      5. input from the vagal and glossopharyngeal nerves via the nearby nucleus of the tractus solitarius modulates activity in the DRG

      Ventral Respiratory Group

      1. The ventral respiratory group (VRG) contains both inspiratory and expiratory neurons.
      2. During normal quiet breathing, the VRG is almost entirely dormant.
      3. During heavy exercise or stress, the VRG sends impulses to the muscles of exhalation and the accessory muscles of inspiration innervated by the vagus nerve.
      4. the neurones of the expiratory VRG are quiescent during tidal respiration, however become active with forced expiration, exercise, etc.
      5. the VRG is divided into 2 divisions,
        1. cranial division – neurones of the nucleus ambiguus
          1. the cranial division innervates muscles of the ipsilateral accessory muscles of respiration, principally via the vagus
        2. caudal division – neurones of the nucleus retroambiguus
          1. the caudal division provides inspiratory and expiratory drive to the motor neurones of the intercostal muscles

      The Pontine Centers

      1. The pontine respiratory centers consist of:
        1. Apneustic center – if unrestrained, sends neural impulses to the DRG that cause prolonged, gasping types of inspiration. It’s located in the caudal part of the pons, and causes slow deep breathing.
          1. situated in the lower pons in the floor of the 4th ventricle, near the middle cerebellar peduncle
          2. impulses from these neurones –> inspiratory DRG and increased “ramp” AP’s
          3. section of the brainstem immediately above this group –> apneusis
          4. prolonged inspiratory gasps interrupted by transient expiratory efforts
          5. this is restrained by the pneumotaxic centre and the inflation reflex
        2. Pneumotaxic center – enhances the rhythmicity of breathing pattern by causing the depth of breathing to decrease and the rate of breathing to increase in almost an equal amount. It’s located in the rostral or upper part of the pons.
          1. located in the upper pons, in the nucleus parabrachialis and the Kolliker Fuse nucleus
          2. acts to limit the activity of the inspiratory DRG
          3. therefore regulating the inspired volume and rate of respiration
          4. acts only as a modulator, as normal respiratory rhythm can exist in its absence
      Advanced Anatomy and Physiology: Respiratory System, Neural Control of Breathing

      Respiratory Component Failure

      1. Several clinical conditions can depress the function of the respiratory components of the medulla.
      2. They include:
        1. reduced blood flow
        2. acute poliomyelitis
        3. CNS depressant drugs

      Monitoring Systems of Medulla Rhythmicity Center

      1. The major known monitoring systems that act on the medulla (DRG and VRG) are the:
          1. central chemoreceptors
          2. peripheral chemoreceptors

      Central Chemoreceptors

      1. situated near (beneath) the ventral surface of the medulla, near the origins of the vagi and glossopharyngeal nerves
      2. The most powerful stimulus known to influence the respiratory components of the medulla is an excess concentration of hydrogen ions [H+] in the CSF.
      3. The central chemoreceptors are responsible for monitoring the H+ ion concentration of the CSF.
      4. Increased PaCO2 also causes cerebral vasodilatation which enhances diffusion of CO2
        into the CSF and brain ECF
      5. A portion of the central chemoreceptors is actually in contact with the CSF.
        1. these are anatomically separate from the respiratory centers, and are bathed in brain ECF, the composition of which is determined by CSF, blood flow and local metabolism
      Central Chemoreceptors

      Monitoring Mechanism

      1. Central chemoreceptors transmit signals to the medulla by the following mechanism:
        1. as CO2 levels increase in the arterial blood, the CO2 molecules diffuse across a semipermeable membrane, called the blood-brain barrier, which separates the blood from the CSF
        2. the blood-brain barrier is very permeable to CO2 molecules and relatively impermeable to H+ and HCO3- ions
      2. The H+ ion generated from the CO2 combined with water in the CSF to diffuse into bicarbonate and H+ rapidly increase and significantly reduces pH in the CSF.
      3. The liberated H+ ions cause the central chemoreceptors to transmit signals to the respiratory component of the medulla, which, in turn, increases alveolar ventilation.
      4. The increased ventilation reduces CO2 in the blood and subsequently CSF.

      Peripheral Chemoreceptors

      1. The peripheral chemoreceptors are special oxygen-sensitive cells that react to reductions of oxygen levels in the arterial blood.
      2. They are located high in the neck at the bifurcation of the carotid arteries and on the aortic arch.
      3. The peripheral chemoreceptors are also called carotid and aortic bodies.
      4. Although the peripheral chemoreceptors also monitor changes in PCO2 and PH, they play a more important role in monitoring PO2 levels. These receptors exert little control over ventilation until the PO2 has dropped below 60 mm Hg. Thus hypoxia is the main stimulus for ventilation in persons with chronically elevated levels of CO2. If these patients are given oxygen therapy at a level sufficient to increase the PO2 above that needed to stimulate the peripheral chemoreceptors, their ventilation may be seriously depressed.
      Peripheral Chemoreceptors

      Monitoring Mechanism

      1. The carotid and aortic bodies are composed of epithelial-like cells and neuron terminals in intimate contact with arterial blood.
      2. When activated by a low PaO2 (<60 mm Hg) , sensory signals are transmitted to the respiratory components in the medulla.
      3. Compared to the aortic bodies, the carotid bodies play a much greater role in initiating an increased ventilatory rate in response to reduced PaO2.
      4. Other factors that stimulate the peripheral chemoreceptors include:
        1. decreased pH
        2. hypoperfusion
        3. increased temperature
        4. nicotine
        5. PaCO2

      Responses Activated by Peripheral Chemoreceptors

      1. In addition to increased ventilation activated by the peripheral chemoreceptors, other responses include:
        1. peripheral vasoconstriction
        2. increased pulmonary vascular resistance
        3. systemic hypertension
        4. tachycardia
        5. increase left ventricular performance
      2. Factors effecting extra-alveolar vessels
        1. smooth muscle tone largely determines vessel caliber, therefore,

      image

      Reflexes that Influence Ventilation

      1. A number of reflexes are known to influence the rate of ventilation, they include:
        1. Hering-Bruer Inflation Reflex
        2. Deflation Reflex
        3. Irritant Reflex
        4. Juxtapulmonary-Capillary Receptors
        5. Baroreceptors
        6. Stimuli

      Hering-Bruer Inflation Reflex

      1. The Hering-Bruer inflation reflex is generated by stretch receptors located in the smooth muscle walls of the bronchi and bronchioles that become excited when the lungs overinflate.
      2. These produce sustained discharge on lung inflation (no adaptation)
      3. These stretch receptors send signals to the medulla via the vagus verve, causing inspiration to stop.
        1. Afferents travel in large myelinated fibers of the vagus to the medulla
      4. The Hering-Bruer reflex appears to be a protective mechanism against pneumothorax.
      5. The receptors are stimulated by the rate as well as extent of inflation, and are sensitized by reduced compliance, such as with trilene
      6. Stimulation leads to a decrease, or cessation, of inspiratory muscle activity
      7. May possibly be of some importance in the newborn

      Deflation Reflex

      1. Opposite of the Hering-Breuer reflex
      2. The deflation reflex is stimulated when the lungs are compressed or deflated, causing an increased rate of breathing.
      3. Precise mechanism for this reflex is not known.
      4. Possibly related to the sigh mechanism
      5. Produces an increase in ventilation with a reduction in FRC below normal

      Irritant Reflex

      1. When the lungs are exposed to toxic gases, the irritant receptors may be stimulated.
      2. These irritant receptors are subepithelial mechanoreceptors located in the trachea, bronchi, and bronchioles.
      3. When these receptors are activated, a reflex response causes the ventilatory rate to increase as well as cough and bronchoconstriction.
      4. Discharge in response to nociception, impulses travel in myelinated vagal fibres, –> bronchoconstriction and hyperpnoea
      5. These show rapid adaptation and are involved with mechanoreception

      Juxtapulmonary-Capillary Receptors

      1. J receptors are located in the interstitial tissues between the pulmonary capillaries and the alveoli.
      2. When these J receptors are stimulated, a reflex response triggers rapid, shallow breathing.
      3. Respond very quickly to chemicals injected into the pulmonary circulation
      4. May also possibly respond to chemicals in alveolar air
      5. Impulses travel in slow, non-myelinated vagal fibres, –> rapid, shallow breathing (intense stimulation –> apnoea)
      6. J receptors are activated by:
        1. pulmonary capillary congestion
        2. capillary hypertension
        3. edema – lung deflation
        4. serotonin – emboli
      7. These may be responsible for the hyperpnoea and dyspnoea of CCF and interstitial lung disease

      Baroreceptors

      1. The normal function of the aortic and carotid sinus baroreceptors, located near the aortic and carotid peripheral chemoreceptors, is to initiate reflexes that cause:
        1. decreased heart rate and ventilatory rate in response to an elevated systemic BP
        2. increase heart rate and ventilatory rate in response to a reduced systemic BP
      Regulation of blood pressure with baroreceptors

      Other Stimuli that Affect Ventilation

      1. Many stimuli can influence ventilation:
        1. sudden cold stimulus may lead to arrest
        2. sudden pain may cause arrest, however, prolonged pain may lead to tachypnea
        3. irritation of the pharynx and larynx may trigger arrest followed by coughing
        4. stretching the anal sphincter triggers an increase in respiratory rate
        5. light pressure applied to the thorax may increase ventilation
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