Chapter 16

• Respiration


  3 separate but related functions: 1. ventilation (breathing), 2. gas exchange, 3. oxygen utilization by the tissues in the energy-liberating reactions of cell respiration
• Gas exchange in each lung

  • Occurs across an estimated 300 million air sacs known as pulmonary alveoli
  • Diffusion rate between alveolar air and capillary blood also depends on distance separating them
  • Thickness of average alveolar cell and capillary endothelial cells is about 0.15 micrometers
  • Air-blood distance = 0.3 micrometers
  • Type I alveolar cells comprise 95-97% of total surface area of the lung, gas exchange with blood occurs primarily through type I alveolar cells
• Thoracic cavity


  • The structures in the central region (mediastinum) are enveloped by two layers of wet epithelial membrane collectively called the pleural membranes
  • Superficial later (parietal pleura) lines inside of thoracic wall
  • Deep layer (visceral pleura) covers surface of lungs
• Boyle's law


  The statement that the pressure of a given quantity of a gas is inversely proportional to its volume
• Changes in intrapulmonary pressure

  Occur as a result of changes in lung volume
• Increase in lung volume during inspiration


  Decreases intrapulmonary pressure to subatmospheric levels, air therefore goes in
• Decrease in lung volume


  Raises the intrapulmonary pressure above that of the atmosphere, expelling air from the lungs
• Law of Laplace


  The pressure thus created is directly proportional to the surface tension and inversely proportional to the radius of the alveolus
• Surfactant


  • Alveolar fluid contains a substance that reduces surface tension
  • Secreted into alveoli by type II alveolar cells and consists mostly of phospholipids
  • Primarily phosphatidylcholine and phosphatidylglycerol together with hydrophobic surfactant proteins
• Inspiration and expiration


  1. External intercostal muscles

  2. Internal intercostal muscles

  3. Interchondral part of internal intercostals (parasternal intercostals)
• Spirometry


  • Subject breathes in a closed system in which air is trapped within a light plastic bell floating in water
  • Bell moves up when the subject exhales and down when the subject inhales
  • Movement of the bell causes corresponding movements of a pen, which traces a record of the breathing (spirogram)
• Dyspnea


  Shortness of breath
• Dalton's law


  Total pressure of a gas mixture (such as air) is equal to the sum of the pressures that each gas in the mixture would exert independently
• With increasing altitude


  The total atmospheric pressure and the partial pressure of the constituent gases decrease
• At Denver (5000ft above sea level), the atmospheric pressure is decreased to 619mmHg and the PO2 is therefore reduced to 619 x 0.21 = 130mmHg
• At the peak of Mount Everest (29,000ft), the PO2 is only 42mmHg
• As one descends below sea level, as in scuba diving


  The total pressure increases by one atmosphere for every 33ft
• At 33ft, pressure = 2 x 760 = 1520mmHg
• At 66ft, pressure = 3atms
• Partial pressures of gases in blood


  Because solubility is a constant and the temperature of the blood does not vary significantly, the concentration of a gas dissolved in a fluid such as plasma depends directly on its partial pressure in the gas mixture
• Significance of blood PO2 and PCO2 measurements

  • Because the oxygen carried by RBCs must first dissolve in plasma before it can diffuse to the tissue cells, a doubling of the blood PO2 means that the rate of oxygen diffusion to the tissues would double under these conditions
  • Breathing from a tank of 100% oxygen (PO2 of 760mmHg) would significantly increase oxygen delivery to the tissues, although it would have little effect on the total oxygen content of blood
• Pulmonary circulation


  • Low-resistance, low-pressure pathway
  • Low pulmonary blood pressure produces less filtration pressure than that produced in the systemic capillaries, thus affords protection against pulmonary edema
  • Excessive fluid can enter interstitial spaces of the lungs and alveoli, impeding ventilation and gas exchange, occurs with pulmonary hypertension, may be produced by left ventricular heart failure
• Nitrogen narcosis


  • Increased amounts of nitrogen dissolved in plasma membranes at high partial pressures
  • Resembles alcoholic intoxication, depending on depth of the dive
• Brain stem respiratory centers

  • Respiratory rhythm is generated by a loose aggregation of neurons in ventrolateral region of medulla oblongata, which forms rhythmicity center
• Control of automatic breathing

  • Group of neurons called pre-Botzinger complex in ventrolateral medulla is believed to generate inspiratory rhythm
  • Although it has intrinsic rhythmicity, and its neurons have automatic bursts of activity, the mechanism by which pre-Botzinger complex generates inspiratory rhythm is not fully understood
  • Its automatic rhythm is influenced by both excitatory and inhibitory synapses, and so can be modified by requirements for speech and other motor activities
• Chemoreceptors in the medulla

  • Increase in arterial PCO2 causes an increase in the PCO2 of the CSF, lowering its pH
  • This stimulates central chemoreceptor neurons located in the retrotrapezoid nucleus on the centrolateral surface of the medulla oblongata, near the exit of the 9th and 10th cranial nerves
  • These central chemoreceptors then stimulate breathing via their projections to pre-Botzinger complex of medulla
• Effects of blood PO2 on ventilation

  When blood PCO2 is held constant, PO2 of arterial blood must fall from 100mmHg to below 70mmHg before ventilation is significantly stimulated
• Hypoxic drive


  Due to direct effect of PO2 on carotid bodies
• Effects of pulmonary receptors on ventilation

  Irritant receptors in the wall of the larynx and receptors in the lungs identified as rapidly adapting receptors, can cause a person to cough in response to components of smoke and smog, and to inhaled particulates
• Hemoglobin


  • Most of the oxygen in the blood is contained within RBCs, where it is chemically bonded to hemoglobin
  • Each Hb molecule consists of 4 polypeptide chains called globins and 4 iron-containing, disc shaped organic pigment molecules called hemes
• Oxyhemoglobin dissociation curve


  • Percent oxyhemoglobin saturation at different values of PO2
  • At the steep part of sigmoidal curve, small changes in PO2 values produce large differences in percent saturation
  • Decrease in venous PO2 from 40mmHg to 30mmHg, as might occur during mild exercise, corresponds to a change in percent saturation from 75% to 58%
• Effect of pH and temperature on oxygen transport

  • A decrease in blood pH (increase in H+ concentration) decreases affinity of hemoglobin for oxygen at each PO2 value, resulting in "shift to the right" (Bohr effect)
  • A curve that is shifted to the right has a lower percent oxyhemoglobin saturation at each PO2, and a greater unloading of oxygen to tissues
• Sickle-cell anemia


  • Occurs almost exclusively in people of African heritage
  • Carried in recessive state by 8-11% of African American population, making it the most common monogenic disorder
  • Occurs when a person inherits the affected gene from each parent and produces HbS instead of normal HbA
  • Differs in that one amino acid is substituted for another (valine instead of glutamic acid) in Hb beta chains
  • Single base change in DNA of the beta chain gene
• Myoglobin


  • Red pigment found exclusively in striated muscle cells
  • Slow-twitch, aerobically respiring skeletal fibers and cardiac muscle cells in particular
• Chloride shift


  • Unloading of oxygen is increased by the bonding of H+ released from carbonic acid to oxyhemoglobin
  • Bohr effect results in increased conversion of oxyhemoglobin to deoxyhemoglobin
  • Deoxyhemoglobin bonds H+ more strongly, so act of unloading its oxygen improves ability of Hb to buffer H+ released by carbonic acid
  • Removal of H+ from solution by its bonding to Hb then acts through the law of mass action to favor the continued production of carbonic acid
  • Increases ability of blood to transport CO2
  • CO2 transport enhances oxygen unloading and oxygen unloading improves CO2 transport
• Reversed chloride shift


  • Operates in the pulmonary capillaries to convert carbonic acid to H2O and CO2 gas, which is eliminated in expired breath
  • PCO2, carbonic acid, H+ and bicarbonate concentrations in the systemic arteries are thus maintained relatively constant by normal ventilation
  • Required to maintain acid-base balance of the blood
• Acid-base balance


  • A fall in blood pH below 7.35 = acidosis
  • Blood pH of 7.2 represents serious acidosis
  • A rise in blood pH above 7.45 is called alkalosis
• Neurogenic and humoral mechanisms

  • To explain increased ventilation during exercise
  • Neurogenic: 1. Sensory nerve activity from the exercising limbs may stimulate respiratory muscles either through spinal reflexes or via brain stem respiratory centers, 2. Input from cerebral cortex may stimulate brain stem centers to modify ventilation
• Starting at altitudes as low as 5000ft

  Decreased arterial PO2 stimulates carotid bodies to produce an increase in ventilation
• Hypoxic ventilatory response


  • Increased breathing = hyperventilation
  • Lowers arterial PCO2 and produces respiratory alkalosis
  • Blunts hypoxic ventilatory response