Respiration: Hemoglobin, Environmental Factors, and Ventilation Control

Hemoglobin Structure and Function

  • Hemoglobin consists of heme and four globulin proteins (two alphas, two betas).
  • Each heme contains iron, which binds to O2 or CO2.
  • Red blood cells contain millions of hemoglobin molecules.

Hemoglobin Affinity

  • Adult hemoglobin: two alpha and two beta proteins.
  • Fetal hemoglobin: two alpha and two gamma proteins.
  • Affinity: the desire for binding (loading) and unloading (letting go).
  • High affinity: high desire for attaching, low desire to release.
  • Low affinity: low desire for attaching, high desire to release.

Environmental Factors Affecting Hemoglobin Affinity

  • Plasma and tissues surrounding hemoglobin influence affinity.
  • Factors include PO2 of blood, blood pH, temperature, and metabolic activity of red blood cells.

Hemoglobin Saturation Curve

  • X-axis: PO2 values in millimeters of mercury (mmHg).
  • Y-axis: Percent of O2 saturation of hemoglobin.
  • Saturation curve represents the average of all hemoglobins in the body.
  • No hemoglobin is ever at 100% saturation; values are an average.

Slope and Rate of Change

  • The slope of the saturation curve indicates the rate of change in O2 saturation relative to PO2.
  • Flatter slope: small change in saturation for a large change in PO2.
  • Steeper slope: large change in saturation for a small change in PO2.

Affinity and PO2

  • As PO2 values decrease, hemoglobin's affinity lowers.
  • As PO2 values increase, hemoglobin's affinity increases.

Hemoglobin Structure and Binding

  • Hemoglobin can hold four gas molecules (O2 or CO2).

  • Hb+4O2Hb + 4O_2

  • Chemical binding to proteins causes a change in shape.

  • The first O2 is the hardest to bind due to the tightly packaged hemes.

  • Binding of the first O2 changes the shape, exposing the second iron.

  • Each subsequent O2 is easier to bind, increasing affinity.

Oxygen Release

  • Releasing the fourth O2 makes it easier to release the third, and so on.
  • Adding more O2 increases affinity; removing O2 lowers affinity.

PO2 and Tissue Saturation

  • At a PO2 of 40 mmHg, hemoglobin is 75% saturated.
  • As environmental PO2 values lower, hemoglobin's affinity lowers.
  • As environmental PO2 values increase, hemoglobin's affinity increases.
  • Without affinity variation, the saturation curve would be linear.

The Bohr Effect

  • The Bohr effect is the right shift (compared to pH 7.4) related to the decrease in pH and indicates a decrease in affinity.

  • Acidic environment results in a right shift.

  • pH=[OH−][H+]pH = \frac{[OH^-]}{[H^+]}

  • More hydrogen ions means a lower pH (more acidic).

  • Less hydrogen ions mean a higher pH (more basic).

  • Physical exertion leads to more acidic conditions (lactate and pyruvate production), lowering hemoglobin's affinity.

  • Bohr Effect Graph: The only named effect on the Hemoglobin Saturation Curve.

  • Left Shift: Increase in affinity. Does not have a name.

  • Right Shift: Decrease in affinity. Known as the Bohr effect.

Temperature Effects

  • Normal temperature: 38°C.
  • Higher temperature: right shift, decreased affinity.
  • Lower temperature: left shift, increased affinity.
  • Warmer temperatures and muscular activity lower hemoglobin affinity, delivering more oxygen to active cells.
  • Lowering temperatures slows metabolic rate, retaining oxygen.
  • Reptiles become more active when warmer.

Other Factors

  • Metabolic activity within red blood cells also influences hemoglobin's affinity. The more active the red blood cells are, the lower their affinity.

Fetal Hemoglobin

  • Fetal hemoglobin has two alphas and two gammas, not two betas.
  • Gamma hemoglobin has a higher affinity for oxygen than beta hemoglobin.
  • Allows the fetus to take O2 from maternal blood.

Oxygen Transfer

  • Maternal and fetal blood compete for oxygen across the placental barrier.
  • Gamma hemoglobin in fetal blood has a higher affinity for O2, improving oxygen uptake.

Hemoglobin Saturation Curves Comparison

  • Fetal hemoglobin curve is left-shifted compared to adult hemoglobin, indicating a higher affinity.
  • For any given PO2 value, fetal hemoglobin has a higher affinity for oxygen.
  • Using Green Lines, at PO2 = 27, Mom Hb Saturation=50.

P50 Value

  • P50 value can be thought of as another form of measurement along with the Hemoglobin Saturation Curve graph.
  • Compares hemoglobin affinities by determining the PO2 value at 50% saturation.
  • Fetal hemoglobin has a lower P50 value. At 50% saturation, adult hemoglobin requires 27 PO2. at 50% saturation, fetal hemoglobin requires only 18 PO2.

Respiration and Blood pH

  • Respiration affects blood pH values.

  • CO<em>2+H</em>2O⇌H<em>2CO</em>3⇌H++HCO3−CO<em>2 + H</em>2O \rightleftharpoons H<em>2CO</em>3 \rightleftharpoons H^+ + HCO_3^-

  • CO2 + Water forms Carbonic Acid. Carbonic Acid breaks into Hydrogen ion and Bicarbonate ion.

  • Carbonic anhydrase (CA) is the enzyme that allows this reaction to work a lot faster by breaking down water. (e.g. California is not carbonic anhydrase.)

  • More CO2 leads to more hydrogen ions, lowering pH.

CO2 Transport

  • Three ways that CO2 is transported inside of our cells and blood.
  • 7% dissolved gas in plasma; 23% carried by hemoglobin; 70% in the form of bicarbonate ions.

O2 Transport

  • 3% dissolved as a gas in plasma; 97% bound to hemoglobin.

Ventilation Control

  • Brainstem: Contains Medulla Oblongata (Cardio acceleratory nuclei) and Medulla (Cardio inhibitor nuclei)
  • Respiratory Rhythmicity Center (Pacemaker): Sets the pace for breathing rates. Located in the Medulla. Contains Dorsal Respiratory Group (DRG Inspirtory Center) and Ventral Respiratory Group (VRG Forced Breathing).
  • Phrenic Nerve: Signals come from phrenic nerve down the diaphragm.
  • Normal average respiration rates is about 12 to 15 breaths per minute.

Dorsal Respiratory Group (DRG) - Inspiratory Center

  • Normal quiet inhalation(Eupnea) and Forced Breathing.

Ventral Respiratory Group (VRG)

  • Forced breathing. Inhalation and exhalation. (DOES NOT include normal breathing.)

Pons: Aponeusic Nuclei and Pneumotaxic Nuclei.

  • Adjust the output of the respiratory rhythmicity centers.
  • Regulate respiratory rate and depth.

Chemoreceptors

Central chemoreceptors
  • Monitor PCO2 levels indirectly by monitoring hydrogens. (Also known as a hydrogen ion sensor.)
  • Found in the brainstem (Medulla Oblongata).
Peripheral chemoreceptors
  • Found in the aorta and in the carotids the common carotids.
  • Monitors PO2 levels. Significant changes in PO2 activate receptor.
Baroreceptors - Monitoring Blood Pressure
  • Found int the Carotid and Aorta.
  • When blood pressure falls (hypotension), we're going to increase our respiration rates.
  • When blood pressure increases (hypertension), we're going to decrease our respiration rates in response to baroreceptors.

Sensitivity to changes in PCO2 or PO2

  • The graphs shows that for every single change in PCO2, changes can be observed in ventilation rates. Conversely, arterial PO2 values must drop significantly to get changes in ventilation rates. More sensitive to PCO2.
  • PO2: Graph is J curve as very high rate of inspiration occurs only after dropping to 60. X Axis: Arterial PO2. Y Axis: Minute Ventilation.
  • PCO2: arterial pCO2 are determining ventilation rates. X Axis: Arterial PCO2. Y Axis: Minute Ventilation.
  • Hydrogen: As acidic environment in the blood goes up, minute ventilation rates go up. X Axis: Plasma Hydrogen Ion. Y Axis: Minute Ventilation.
  • Ventilation Rate with Partial Pressure: Once ventilation rate goes up, alveolar partial pressures of O2 goes up. X Axis: Ventilation Rate. Y Axis: Partial Pressure.