Respiration 2

• Hypoventilation


  Low oxygen intake (PAO2 decreases) and carbon dioxide build up (PACO2 increases)

  
• Causes of hypoventilation


  • CNS depressed by drugs or injury
  • Severe upper airway obstruction
  • Damage to the thorax and respiratory muscles
  • Severe lung disease

  
• Hyperventilation


  High oxygen intake (PAO2 increases) and carbon dioxide decreases (PACO2 decreases)

  
• Causes of hyperventilation

  • Hypoxia
  • Metabolic acidosis
  • Increased body temperature
• Frictional resistance


  Air flow through the airways causes frictional resistance
• Frictional resistance in the respiratory system

  • At rest, the upper airway (nose, pharynx and larynx) provides ~60% of the airway resistance
  • Nasal resistance can be decreased via dilation of the external nares and vasoconstriction of the vascular tissue in the nose
  • The total cross-sectional area increases toward the periphery of the lung, the velocity of airflow diminishes from trachea to bronchioles
  • High-velocity turbulent airflow in trachea and bronchi produces the lung sounds heard upon auscultation
  • Laminar airflow in bronchioles produce no sound
  • Larger airways contribute up to 80% of the frictional resistance; bronchioles up to 20%

  
• Smooth muscle contraction


  Smooth muscle activity regulates airway diameter
• Smooth muscle contraction


  1. Parasympathetic nervous system

  2. Vagus nerve

  3. Muscle contraction = narrows trachea, bronchi and bronchioles (bronchoconstriction)
• Bronchoconstriction


  • Bronchospasm mediated by the PNS is a protective mechanism if irritating materials are inhaled
  • Airway smooth muscle contracts in response to inflammatory mediators, e.g. histamine

  
• Smooth muscle relaxation and dilation

  1. Epinephrine (from adrenal medulla) act on β2–adrenergic receptors

  2. Norepinephrine from sympathetic nervous system act on β2–adrenergic receptors
• Gas exchange


  Lung receives blood flow from 2 circulatory systems: pulmonary circulation and bronchial circulation
• Gas exchange


  1. Ventilation brings O2 to the alveoli and removes CO2

  2. O2 is consumed in the tissues, so a pressure difference exists for its diffusion from alveoli to venous blood and from arterial blood to the tissues

  3. CO2 is produced in the tissues, so a pressure difference exists for its diffusion from tissue to blood and from venous blood to the alveoli

  
• Ventilation-perfusion (V/Q) matching


  • Ideally, each alveoli should receive air and blood in amounts that are optimal for gas exchange
  • V/Q mismatch occurs in normal, healthy lungs due to branching pattern of bronchi and blood vessels and gravity
  • In lung diseases, V/Q mismatch becomes more extreme, can lead to hypoxemia
  • Healthy animals: V/Q ratios close to 1
  • Alveoli with low V/Q ratios are overperfused and underventilated
  • Alveoli with high V/Q ratios have high ventilation in relation to blood flow

  
• Oxygen transport


  • Reversibly bound to haemoglobin (~98%)
  • Dissolved in the water of plasma and RBC (~2%)

  
• Oxygen-haemoglobin binding


  1. Binding of the 1st O2 molecule induces change in the shape of the Hb which increases its ability to bind to the other 3 O2 molecules

  2. In the presence of dissolved CO2, the pH of the blood changes; this causes another change in the shape of Hb, which increases its ability to bind CO2 and decreases its ability to bind O2

  3. With the loss of the 1st O2 molecule, and the binding of the 1st CO2 molecule, another change in shape occurs, which further decreases the ability to bind O2 and increases the ability to bind CO2

  
• Oxygen-haemoglobin dissociation curve


  • A curve that plots the proportion of Hb in its saturated (oxygen-laden) form on the vertical axis against the O2 tension on the horizontal axis
  • Relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2)
  • Determined by "haemoglobin affinity for oxygen"

  
• Shifts of the oxygen-haemoglobin dissociation curve

  • Right shift: Decreased affinity of Hb for O2 - more difficult for Hb to bind to O2 but it makes it easier for the Hb to release O2 bound to it
  • Left shift: Increased affinity of Hb for O2 e.g. at the lungs - Hb has an increased affinity for O2 and unloads it more reluctantly

  
• Bohr's effect


  • O2 binding affinity of Hb is inversely related to the concentration of CO2 and H+ concentration
  • At tissue: Increased PCO2 and H+ concentration right shift
  • At lungs: Decreased PCO2 and H+ concentration left shift
  • Bohr's effect facilitates O2 release from Hb at tissues and O2 uptake by Hb at lungs

  
• Carbon dioxide transport


  • Dissolved in plasma (~5%)
  • Bound to proteins, particularly Hb (~15%)
  • Buffered with water as carbonic acid (~80%)

  
• Carbon dioxide transport


  1. CO2 combines with the terminal uncharged amino groups (R-NH2) to form carbamino compounds (in proteins) or carbaminohaemoglobin (in Hb)

  2. CO2 diffuses into the red blood cells

  3. Carbonic anhydrase within the RBCs quickly converts the carbon dioxide + water = carbonic acid

  4. Carbonic acid dissociates into bicarbonate ions and hydrogen ions

  5. The bicarbonate ion is transported out of the red blood cell into plasma in exchange for a chloride ion (chloride shift)

  6. Hb binds to the free H+

  7. When the blood reaches the lungs, the bicarbonate ion is transported back into the red blood cell in exchange for the chloride ion

  8. The H+ dissociates from the Hb and binds to the bicarbonate ion

  9. This produces carbonic acid, which is converted back into CO2 through the enzymatic action of CA

  10. CO2 is expelled through the lungs during exhalation

  
• Haldane effect


  • Describes the ability of Hb to carry increased amounts of CO2 in the deoxygenated state as opposed to the oxygenated state
  • A high concentration of CO2 facilitates dissociation of oxyhaemoglobin

  
• Gas transport during exercise

  • Oxygen demands are met by increasing blood flow, Hb levels and O2 extracted from the blood
  • More capillaries become perfused by blood diffusion increases
  • Decrease in pH, increase in temperature and increase in PCO2 decrease Hb affinity for oxygen release O2 to active muscle cells