How is the Davenport nomogram used when PCO2 is constant?
pH is on the x-axis and HCO3- concentration (mm/L) is on the y-axis. Using the HH equation and holding PCO2 constant, one can calculate all of the pH and corresponding HCO3- concentrations possible for that value of PCO2. The line that is generated on the Davenport nomogram for a constant PCO2 is called an isobar (isobar=constant pressure).
Explain the changes in pH, PCO2, and HCO3- when a non-carbonic acid is added to the body. Visualize what the Davenport nomogram would look like.
Explain the same scenario for when a base is added to the body.
Suppose 1meq/L of H+ (from a strong NC acid) was added to the body. H+ would first be buffered by extracellular HCO3 – (NC buffers will react more slowly). Plasma H+ would increase and HCO3 - would decrease. But, the respiratory system holds PCO2 constant-it will not change if respiration is normal!
HNC → H+ + NC
CO2 + H2O ← H2CO3 ← H+ + HCO3 -
If H+ had been removed (which is equivalent to adding base that combines with the blood H+ ), the change would follow the green arrow, in FIGURE 7 (attached); if respiration is normal, PCO2 does not change. The combined arrows lie on PCO2 = 40, a CO2 isobar. The values of HCO3 – and pH correspond to those given by the HH equation for the CA system, with H2CO3 = 0.03 u 40 = 1.2 meq/L so that pH = 6.1 + log (HCO3 – /1.2).
Whenever NCA is buffered:
• PCO2 is constant and
• pH and HCO3 – change by sliding up or down an isobar in the Davenport nomogram.
Imagine an instance where PCO2 increases due to abnormal respiratory function (hypoventilation).
How the values of pH and bicarb change as a result?
What buffering system plays a predominant role in this instance? What effect does this buffering system have????
Explain the same values if PCO2 increases (hyperventilation).
Picture the Davenport nomogram in these instances.
Suppose PCO2 (i.e., H2CO3) were to increase because of abnormal respiratory function.
• The values of HCO3 - and pH would no longer lie on the PCO2 = 40 isobar.
• The added CA will be titrated by NC buffers only. Hb is the principal blood NC buffer system and CA is buffered first by it.
↑CO2 + H2O → H2CO3 → H+ + HCO3 -
HHb ← H+ + Hb-
Without buffering to remove H+ from solution, adding H2CO3 yields an insignificant amount (nanomoles) of bicarbonate since weak acids ionize poorly. But, each H+ (from CA) that is buffered by Hb– (or by another NC buffer base), shifts the CO2 reaction to the right and causes one HCO3 – to be produced. Therefore, the change in [HCO3 – ] is almost completely determined by the amount of CA buffered by the NC buffer system, initially by Hb. The amount of HCO3 – produced equals the amount of Hb– lost.
The normal buffer capacity of Hb is about –11 slykes (sl). (1 sl = 1 mM change in [HCO3 – ] per unit change in pH). That means that if PCO2 increases enough to decrease pH by 1 unit, Hb– will buffer enough H+ to raise the plasma HCO3 – concentration by 11 mM.
PCO2 increases to the value that the individual’s abnormal respiratory system establishes and will be constant when that value is reached until the problem is reversed or eliminated.
If the person’s problem had been hyperventilation , PCO2 and [HCO3 – ] would have decreased and pH would have increased, again at the rate of –11 sl (decrease in [HCO3 – ] of 11 mM for each unit increase in pH). In this case, the conjugate base of the CA system, HCO3 – , is reacting with (neutralizing) HHb, the acid form of the NC buffer.
Whenever PCO2 changes,
• CA increases or decreases and
• pH and HCO3 – change by sliding up or down a line with slope –11 in the Davenport nomogram. (The slope of this line depends of [Hb], but we will assume –11 for this class.)
Fill in the following table. Explain your answers. State what kind of acid-base disorder is caused by each of the changes (metabolic acidosis, respiratory alkalosis, etc.).
It is clear that buffering a change of CA has quite different consequences from buffering a change in HNC:
• Adding HNC leaves PCO2 unaffected and lowers [HCO3 – ] while causing an acidosis (metabolic).
• Increasing CA (always produced by increasing PCO2) raises [HCO3 – ] while causing an acidosis (respiratory). FIGURE 8, dashed arrow
• Opposite changes occur with alkalosis.
buffering rules summarized
What is anion gap?
In what type of acid-base disorder may there be an anion gap? What causes the anion gap in this case?
What are some endogenous and exogenous causes of anion gap?
Explain the definitiveness of anion gap in diagnosing this type of acid-base disorder.
In body fluids there is charge neutrality: the number of anions = number of cations. In lab reports, usually only the major ions are measured. In that case, there seems to be a difference between the concentration of cations and the concentration of anions.
Na+ = 140 mM
Cl- = 100 mM
HCO3 - = 24 mM
Total 124 mM
This difference of 16 mM represents the difference between the unmeasured cations and anions. The unmeasured cations are less than the unmeasured anions, and the difference is called the anion gap. The anion gap is used to show changes in the concentration of unmeasured ions. In metabolic acidosis, the added acid dissociates into H+ and an anion NC– . The H+ is buffered in part by HCO3 – (reaction (1)) lowering H+ concentration to near zero and generally lowering the HCO3 – concentration (which is counted in the anion gap). The added anion NC– remains, but is not measured (i.e., not counted in the anion gap). Hence, the anion gap gets larger.
The following buffering reactions rapidly take place in the venous blood.
HNC → H+ + NC-
CO2 + H2O ← H2CO3 ← H+ + HCO3 -
HHb ← H+ + Hb-
The CA buffering during a metabolic acidosis affects an important clinical measurement of the “anion gap.” Endogenous acids that can increase the anion gap:
• HSO4 – accumulates in renal failure
• lactic acid accumulates in hypoxemia
• ketones accumulate in diabetes mellitus
Acid metabolites of exogenous materials can also increase the anion gap- methanol and ethylene glycol poisoning
NOTE: There are some metabolic acidosis that do not have an increase in the anion gap, for example when the NC base is Cl– . (You will learn about this in the iHuman case.)
The take-home message: increased anion gap may indicate a metabolic acidosis (it is not definitive).