1. General Features (for most animals)
    1. Breathing movements
      1. Fresh supply of air/water at respiratory surface
      2. Keeps a large diffusion gradient across the shortest possible distance
    2. Diffusion of oxygen and carbon dioxide across the respiratory epithelium
      1. Thin layers (.5-15m m thick)
      2. Large surface area (human lungs 50-100 square meters)
      3. Carbon dioxide out, oxygen in
    3. Transport of gases by blood
      1. High oxygen conc in systemic arteries, pulmonary veins
      2. High carbon dioxide concentration in systemic veins, pulmonary arteries
      3. Insects use a tracheal system, allowing direct exchange with tissues (no blood needed)
    4. Diffusion of gases across capillary walls (to / from blood and cells)
    5. Rates of exchange are dependent on metabolism
      1. Increased metabolism means more aerobic enzymes, more cristae, and mitochondria
  2. Oxygen and carbon dioxide in blood
    1. Respiratory pigments (eg hemoglobin)
      1. Combine with oxygen to increase the blood oxygen content
        1. color changes when oxygen binds
        2. .3% volume w/out hemoglobin, 20% volume with hemoglobin
      2. some fishes don't have respiratory pigments, but they live in arctic waters
        1. lower metabolic rate
        2. oxygen has a higher solubility at lower temperatures
      3. hemoglobin - four oxygen molecules bind to four heme units
        1. oxyhemoglobin - oxygenated
        2. deoxyhemoglobin - deoxygenated
        3. carboxyhemoglobin - carbon monoxide is bound (200 x greater affinity that oxygen)
    2. Oxygen transport in blood
      1. Capacity is equal to content when the blood is saturated (all sites are bound to oxygen)
        1. Content is equal to the amount of oxygen in solution (a very small portion) plus the bound oxygen)
        2. Because capacity differs among individuals, content is expressed as % saturation
        3. Oxygen dissociation curves (fig 13-4) demonstrate the % saturation as a result of the partial pressure of oxygen
          1. Sigmoidal shape reflects the subunit cooperativity (first molecule of oxygen has a harder time binding)
          2. Curves shift right, indicating a decreased hemoglobin-oxygen affinity
            1. Increased temperature
            2. Increased binding of DPG, ATP, and GTP
            3. Decreased pH (acidic) - Bohr effect
            4. Increased carbon dioxide concentration
    3. Carbon dioxide transport in the blood (fig 13-9)
      1. Combines with water to form carbonic acid, and hydrogen and bicarbonate ions
        1. Bicarbonate is the major form of carbon dioxide at normal pH
      2. Forms carbamino compounds with NH2 groups on hemoglobin as well as other proteins
      3. Total carbon dioxide content is the carbon dioxide in all its forms
      4. At any give PCO2, a decrease in pH will cause a decrease in bicarbonate ion (buffering function, combines with extra H ions, see fig 13-10)
    4. Transfer of gases to and from blood
      1. Carbonic anhydrase - enzyme which catalyzes CO2 + H2O to H+ + HCO3- (reversibly)
        1. In red blood cells (13-11)
        2. In endothelial cells of capillaries (13-12)
  3. Regulation of Body pH
    1. Normal = 7.4, but body can function in range of 7.0 - 7.8
    2. Affected by CO2 /HCO3- and NH3/ NH4+ levels
    3. Hydrogen ion production and excretion
      1. Increased carbon dioxide leads to decreased pH (respiratory acidosis)
      2. Low carbon dioxide leads to increased pH (respiratory alkalosis)
      3. Consuming food leads to an overall increase in hydrogen ions
      4. Acid leaves the body via the kidneys and gills
      5. pH of blood closest to the pK of plasma proteins, which makes them the most important buffer, but bicarbonate is a more easily regulated buffer
        1. increased respiration decreases carbon dioxide and increases blood pH
        2. kidneys are able to excreet bicarbonate which lowers blood pH
      6. ions and pH - must maintain electroneutrality
        1. increased bicarb causes a decrease in chloride or an increase in sodium ions
        2. vomiting from the stomach decreases chloride ions causing an increase in bicarb (metabolic alkalosis)
        3. vomiting from the duodenum decreases bicarb ions (metabolic acidosis)
    4. Factors influencing intracellular pH
      1. Acid is buffered by proteins/other physical buffers
      2. Carbonic anhydrase can create CO2 which diffuses out of the cell
      3. Hydrogen ions can be transported out of the cell (actively or passively)
      4. Na/H and HCO3/ Cl exchange mechanisms
      5. A decreased pH prevents some enzymes from working, therefore metabolism is slowed and fewer H ions are produced while the cell tries to stabilize itself
    5. Factors influencing body pH
      1. Mammalian kidney can excreet acid or base
      2. Aquatic animals excreet acid and use HCO3/ Cl exchangers on external surfaces
      3. Redistribution of hydrogen ions (muscle will absorb H in a sudden pH change, and slowly release them)
      4. Temperature affects dissociation of hydrogen ions from proteins, fortunately the pK of proteins changes in the same manner so there is no overall effect of a change in temp (13-18)
  4. Gas transfer in Air
    1. Functional anatomy of the lung
      1. Respiratory surface area increases with and increase in body weight (13-20)
      2. Mammalian lung (13-21)
        1. Trachea
        2. Bronchi
        3. Bronchiole to terminal bronchiole to respiratory bronchiole
        4. Alveolar duct to alveolar sac to alveolus
      3. Barriers to gas exchange between environment and blood
        1. Aqueous surface + alveolar epithelial cell + interstitial layer + capillary endothelium + RBC wall
        2. Dead space - areas where gas exchange cannot occur
          1. Anatomical - trachea to non-respiratory bronchioles - where no gas exchange could occur as a result of the anatomy
          2. Physiological - anatomical DS plus any place where gases aren't being effeciently exchanged in alveolar areas
      4. Breathing volumes (13-23)
        1. Tidal volume - air moving in and out with regular breathing
        2. Residual volume - air which always remains in the lungs
        3. Vital capacity - total lung volume minus the residual volume
    2. Pulmonary circulation
      1. Bronchial circulation - actually part of the systemic circulation, similar to the coronary circulation in purpose - providing gas/metabolite exchange to dead space areas
      2. Pulmonary circulation - gas exchange for blood going to the rest of the body
        1. Lower pressures to prevent fluid from leaving the capillaries and increasing the diffusion barrier
        2. More blood flows at the base of the lung when standing as a result of gravity
        3. Thoraco-abdominal pump= the reduction in pressure during inhalation also helps return blood to the heart.
        4. Constriction in response to low oxygen areas channels blood to well ventilated areas (for best gas exchange)
    3. Ventilation
      1. Mammals - diaphragm primarily responsible for creating the negative pressure required for breathing, pulls air into lungs
      2. Birds - air sacs, attached to lungs are squeezed and relaxed to create positive/negative pressure to move air
      3. Reptiles - ribs move out to create negative pressure
      4. Frogs - air is pulled (negative pressure) into buccal cavity, then forced into lungs
    4. Pulmonary surfactant - reduce surface tension along lung wall (a lack of the surfactant causes respiratory distress syndrome, especially common in preemies)
    5. Insect tracheal system
      1. System of air-filled tubes going directly to cells - uses rapid diffusion of gases in air - no blood or fluid involved until the very last step
      2. Larger insects can generate air flow in the tracheal system by changing trachea size or by body wall expansion
      3. In many cases the spiracles (openings) can open and close to regulate air flow, fluid loss, and protect against environmental factors
      4. Tracheols (fine endings of tracheal system) are very close to the cells, and filled with fluid most of the time which contains dissolved oxygen
  5. Gas transfer in water : Gills
    1. Flow and gas exchange
      1. Unidirectional flow of water across gills (in mouth, out gills)
      2. Countercurrent flow of blood most common, and often most efficient
      3. High ventillation rate needed as water contains less oxygen than air
    2. Anatomy (13-45)
      1. Gill arches each have two rows of filaments covered with lamellae on top and bottom - increased surface area
      2. Out of water, gills collapse and fish may suffocate
      3. Act as a kidney (ion regulation) and lungs (gas exchange)
  6. Regulation of gas transfer and respiration
    1. Ventilation- perfusion ration
      1. Must match ventilation (oxygen) with perfulsion (blood capacity and flow) to be efficient
      2. Can change where the blood flows to alter this ratio, as well as the amount and rate of ventilation
    2. Neural regulation of breathing
      1. Medullary respiratory center
        1. Controls muscles used in breathing
        2. Integrates all factors and responds with a change in depth and rate of breathing (13-51)
          1. Stretch receptors in lungs
          2. Chemoreceptors for oxygen and carbon dioxide in carotid and aortic bodies
          3. Chemoreceptors for pH of cerebrospinal fluid in medulla
  7. Respiratory response to extreme conditions - You are responsible for reading this section on your own
  8. Swimbladders and Oxygen accumulation
    1. Help increase buoyancy in fish, decreasing energy expenditure required to stay afloat
    2. Rete mirabile - reduces the loss of gas from the swimbladder
    3. Gas gland (fig 13-58 and 13-59) adds oxygen to the swimbladder
      1. A decrease in pH (due to an increase in carbon dioxide) causes oxygen to be released from the hemoglobin
      2. High ion concentrations decrease oxygen solubility which forces the oxygen into the swimbladder